bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a hospital admission survey to estimate the burden of influenza‐associated severe acute respiratory infection in one province of Cambodia—methods used and lessons learned
Authors: Stewart Rebekah J. , Ly Sovann , Sar Borann , Ieng Vanra , Heng Seng , Sim Kheng , Machingaidze Chiedza , Roguski Katherine , Dueger Erica , Moen Ann , Tsuyuoka Reiko , Iuliano A. Danielle
Published: February 2018

Background

Understanding the burden of influenza‐associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza‐associated SARI rates requires hospital‐based surveillance data and a population‐based denominator, which can be challenging to determine.

Objectives

We present an application of the World Health Organization's recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza‐associated SARI, with lessons learned to help others calculate similar estimates.

Methods

Using an existing SARI surveillance platform in Cambodia, we counted influenza‐associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual‐derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case‐patients resided. We used HAS methods to adjust the district‐level population denominator for the sentinel site and calculated the incidence rate of influenza‐associated SARI by dividing the number of influenza‐positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned.

Results

We estimated an adjusted influenza‐associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza‐associated SARI cases in Svay Rieng Province after extrapolation.

Conclusions

Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza‐associated SARI.
Multiple stressors facilitate the spread of a non‐indigenous bivalve in the Mediterranean Sea
Authors: Sarà Gianluca , Porporato Erika M.D. , Mangano Maria Cristina , Mieszkowska Nova
Published: February 2018

Aim

The introduction of non‐indigenous species (NIS) via man‐made corridors connecting previously disparate oceanic regions is increasing globally. However, the environmental and anthropogenic factors facilitating invasion dynamics and their interactions are still largely unknown. This study compiles and inputs available data for the NIS bivalve Brachidontes pharaonis across the invaded biogeographic range in the Mediterranean basin into a species distribution model to predict future spread under a range of marine scenarios.

Location

Mediterranean Sea.

Methods

A systematic review produced the largest presence database ever assembled to inform the selection of biological, chemical and physical factors linked to the spread of B. pharaonis through the Suez Canal. We carried out a sensitivity analysis to simulate current and future trophic and salinity scenarios. A species distribution model was run to determine key drivers of invasion, quantify interactive impacts arising from a range of trophic states, salinity conditions and climatic scenarios and forecast future trajectories for the spread of NIS into new regions under multiple‐parameter scenarios (based on the main factors identified from the systematic review).

Results

Impacts on invasion trajectory arising from climate change and interactions with increasing salinity from the new opening of the canal were the primary drivers of expansion across the basin, the effects of which were further enhanced by eutrophication. Predictions of the current distribution were most accurate when multiple stressors were used to drive the model. A habitat suitability index developed at a subcontinental scale from model outputs identified novel favourable conditions for future colonization at specific locations under 2030 and 2050 climatic scenarios.

Main conclusions

Future expansion of B. pharaonis will be enhanced by climate‐facilitated increased sea temperature, interacting with increasing pressures from salinity and eutrophication. The spatially explicit risk output maps of invasions represent a powerful visual product for use in communication of the spread of NIS and decision‐support tools for scientists and policymakers. The suggested approach, the observed distribution pattern and driving processes can be applied to other NIS species and regions by providing novel forecasts of species occurrences under future multiple stressor scenarios and the location of suitable recipient habitats with respect to anthropogenic and environmental parameters.
An intercontinental comparison of niche conservatism along a temperature gradient
Authors: Vetaas Ole R. , Grytnes John‐Arvid , Bhatta Kuber P. , Hawkins Bradford A.
Published: February 2018

Aims

Phylogenetic niche conservatism (PNC) predicts that closely related species will have similar distributions along major environmental gradients, e.g. temperature. We test this theory by comparing the central tendencies of temperature for selected woody genera, and investigating whether these genera have a similar rank order (sequence) across continents and hemispheres. A strong correlation may indicate niche conservatism, as inherited temperature tolerance would best explain a positive correlation.

Location

Peru (Andes) and Nepal (Himalaya).

Methods

Elevation and temperature ranges for all species belonging to eight disjunct genera of woody plants were compiled. Central tendencies of congeneric species along the temperature gradient were established by means of reciprocal averaging and weighted average temperature. We correlated the rank order of genera from the Himalaya and Andes, and tested if the order in the Himalaya could predict the order in the Andes, using permutation procedure.

Results

Most genera exhibit a bell‐shaped or curvilinear pattern with the maximum number of congeneric species in the centre of the temperature range, but some curvilinear responses and monotonic increases are found in Andes. The order of generic optima along the temperature gradient in each region is highly correlated (ρ > 0.81), as well as the size of the temperature range and minimum temperature limit (ρ > 0.90).

Conclusion

The analyses verify the conjecture that the maximum number of congeneric species is found towards the centre of the temperature range of the genus. This may be caused by newly evolving species not dispersing very far from their ancestors and inherent temperature tolerances. Inherent temperature tolerance and covariates such as primary production and soil conditions are the main factors that may explain consistency of the rank order of disjunct genera along temperature gradients between continents and hemispheres. Hence temperature tolerances within a clade are conserved over time and space.
Cross‐cultural comparison of predictors for self‐care behaviors in patients with type 2 diabetes
Authors: Ikeda Kaori , Fujimoto Shimpei , Morling Beth , Ayano‐Takahara Shiho , Harashima Shin‐ichi , Uchida Yukiko , Inagaki Nobuya
Published: February 2018

The aim of the present study was to evaluate how culture moderates the behavioral and psychosocial predictors of diabetes self‐care activities. Patients with type 2 diabetes were recruited in the outpatient department at two sites: Kyoto University hospital in Japan and the Christiana Care Health System in the USA. The data were collected by survey using questionnaires including questions on the frequency of self‐care activities, behavioral and psychosocial predictors, and other background information from 149 Japanese patients and 48 American patients. The cultural impact was observed by multiple regression analyses with interaction terms on the association between emotional support and self‐care activities in diet in female patients. The findings of the present study serve as an example of how cultural context can affect patients with diabetes, and lead to a better understanding of culturally sensitive behavioral intervention.
Real Options Models of the Firm, Capacity Overhang, and the Cross Section of Stock Returns
Authors: ARETZ KEVIN , POPE PETER F.
Published: February 2018

We use a stochastic frontier model to obtain a stock‐level estimate of the difference between a firm's installed production capacity and its optimal capacity. We show that this “capacity overhang” estimate relates significantly negatively to the cross section of stock returns, even when controlling for popular pricing factors. The negative relation persists among small and large stocks, stocks with more or less reversible investments, and in good and bad economic states. Capacity overhang helps explain momentum and profitability anomalies, but not value and investment anomalies. Our evidence supports real options models of the firm featuring valuable divestment options.
Prognostic importance of FGF2 and FGFR1 expression for patients affected by ameloblastoma
Authors: Fonseca Felipe Paiva , Monteiro Benites Bernar , Soares Ciro Dantas , de Lima Morais Thayná Melo , do Amaral‐Silva Gleyson Kleber , de Almeida Oslei Paes , Soares Fernando Augusto , Fregnani Eduardo Rodrigues
Published: February 2018

Background

Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few are known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study was to investigate whether the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior.

Methods

Fifty‐eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters regarding sex, age, tumor size, duration and location, treatment, recurrences, radiographic features, cortical disruptions, and follow‐up data were obtained from patients' medical records and correlated with the molecules expression. Univariate and multivariate Cox regression analyses were used to investigate the prognostic potential of the biomarkers.

Results

Forty‐four cases (75.9%) exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the columnar peripheral cells, and 43 cases (74.1%) were positive for both. Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P = .05). However, univariate and multivariate analyses did not demonstrate a significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5‐year disease‐free survival (DFS) rate (P = .27, P = .33, and P = .25, respectively).

Conclusion

Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS.
Melatonin protects against defects induced by deoxynivalenol during mouse oocyte maturation
Authors: Lan Mei , Han Jun , Pan Meng‐Hao , Wan Xiang , Pan Zhen‐Nan , Sun Shao‐Chen
Published: February 2018

Deoxynivalenol (DON) is one of the most prevalent fusarium mycotoxins in feedstuff and food. DON causes detrimental effects on human and animal reproductive systems by inducing oxidative stress and apoptosis. However, melatonin is a multifunctional endogenous hormone that plays crucial roles in the development of animal germ cells and embryos as a robust deoxidizer. In this study, we explored the effects of melatonin on the DON exposure mouse oocytes. Our in vitro and in vivo results showed that DON adversely affected mouse oocyte maturation and early embryo cleavage, while melatonin administration ameliorated the toxic effects of DON. DON exposure disrupted the meiotic spindle formation and kinetochore‐microtubule attachment, which induced aneuploidy in oocytes. This might be through DON effects on the acetylated tubulin level. Moreover, we found that DON exposure caused the alteration of DNA and histone methylation level, which might affect early embryo cleavage. The toxic effects of DON on oocytes might be through its induction of oxidative stress‐mediated early apoptosis, while the treatment with melatonin significantly ameliorated these phenotypes in DON‐exposed mouse oocytes. Collectively, our results indicated the protection effects of melatonin against defects induced by DON during mouse oocyte meiotic maturation.
Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin‐induced apoptosis in neural cancer cells
Authors: Yu Zhenlong , Tian Xiangge , Peng Yuling , Sun Zheng , Wang Chao , Tang Ning , Li Bin , Jian Yuqing , Wang Wei , Huo Xiaokui , Ma Xiaochi
Published: February 2018

Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the antitumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH‐SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells. Interestingly, the inhibitory effect of melatonin on proliferation in SH‐SY5Y cells is more potent than that in U118 cells. In contrast, this inhibitory effect on the normal cells is absent. The antitumor effects of melatonin are positively associated with its metabolite N‐acetylserotonin (NAS). Unexpectedly, CYP1B1 is, for first time, identified to localize in the mitochondria of tumor cells, and it metabolizes melatonin to form NAS in situ, which subsequently triggers mitochondria‐dependent apoptosis in cancer cells. In normal cells, NAS does not induce apoptosis. A remarkable individual variation on CYP1B1 expression was also detected in human tumor tissue. These findings provide the novel mechanisms regarding the antitumor effects of melatonin in the level of mitochondria. Thus, we hypothesize that CYP1B1 overexpression in mitochondria would significantly enhance the antitumor effects of melatonin. Mitochondrial CYP1B1 can potentially serve as a specific target to modify the therapeutic and biological effects of melatonin on cancer patients.
The role of climate, forest fires and human population size in Holocene vegetation dynamics in Fennoscandia
Authors: Kuosmanen Niina , Marquer Laurent , Tallavaara Miikka , Molinari Chiara , Zhang Yurui , Alenius Teija , Edinborough Kevan , Pesonen Petro , Reitalu Triin , Renssen Hans , Trondman Anna‐Kari , Seppä Heikki
Published: February 2018

Questions

We investigated the changing role of climate, forest fires and human population size in the broad‐scale compositional changes in Holocene vegetation dynamics before and after the onset of farming in Sweden (at 6,000 cal yr BP) and in Finland (at 4,000 cal yr BP).

Location

Southern and central Sweden, SW and SE Finland.

Methods

Holocene regional plant abundances were reconstructed using the REVEALS model on selected fossil pollen records from lakes. The relative importance of climate, fires and human population size on changes in vegetation composition was assessed using variation partitioning. Past climate variable was derived from the LOVECLIM climate model. Fire variable was reconstructed from sedimentary charcoal records. Estimated trend in human population size was based on the temporal distribution of archaeological radiocarbon dates.

Results

Climate explains the highest proportion of variation in vegetation composition during the whole study period in Sweden (10,000–4,000 cal yr BP) and in Finland (10,000–1,000 cal yr BP), and during the pre‐agricultural period. In general, fires explain a relatively low proportion of variation. Human population size has significant effect on vegetation dynamics after the onset of farming and explains the highest variation in vegetation in S Sweden and SW Finland.

Conclusions

Mesolithic hunter‐gatherer populations did not significantly affect vegetation composition in Fennoscandia, and climate was the main driver of changes at that time. Agricultural communities, however, had greater effect on vegetation dynamics, and the role of human population size became a more important factor during the late Holocene. Our results demonstrate that climate can be considered the main driver of long‐term vegetation dynamics in Fennoscandia. However, in some regions the influence of human population size on Holocene vegetation changes exceeded that of climate and has a longevity dating to the early Neolithic.
Dual transcriptomics reveals co‐evolutionary mechanisms of intestinal parasite infections in blue mussels Mytilus edulis
Authors: Feis Marieke E. , John Uwe , Lokmer Ana , Luttikhuizen Pieternella C. , Wegner K. Mathias
Published: February 2018

On theoretical grounds, antagonistic co‐evolution between hosts and their parasites should be a widespread phenomenon but only received little empirical support so far. Consequently, the underlying molecular mechanisms and evolutionary steps remain elusive, especially in nonmodel systems. Here, we utilized the natural history of invasive parasites to document the molecular underpinnings of co‐evolutionary trajectories. We applied a dual‐species transcriptomics approach to experimental cross‐infections of blue mussel Mytilus edulis hosts and their invasive parasitic copepods Mytilicola intestinalis from two invasion fronts in the Wadden Sea. We identified differentially regulated genes from an experimental infection contrast for hosts (infected vs. control) and a sympatry contrast (sympatric vs. allopatric combinations) for both hosts and parasites. The damage incurred by Mytilicola infection and the following immune response of the host were mainly reflected in cell division processes, wound healing, apoptosis and the production of reactive oxygen species (ROS). Furthermore, the functional coupling of host and parasite sympatry contrasts revealed the concerted regulation of chitin digestion by a Chitotriosidase 1 homolog in hosts with several cuticle proteins in the parasite. Together with the coupled regulation of ROS producers and antagonists, these genes represent candidates that mediate the different evolutionary trajectories within the parasite's invasion. The host–parasite combination‐specific coupling of these effector mechanisms suggests that underlying recognition mechanisms create specificity and local adaptation. In this way, our study demonstrates the use of invasive species’ natural history to elucidate molecular mechanisms of host–parasite co‐evolution in the wild.
Insights into transcriptional silencing and anti‐silencing in Shigella flexneri: a detailed molecular analysis of the icsP virulence locus
Authors: Weatherspoon‐Griffin Natasha , Picker Michael A. , Pew Krystle L. , Park Hiromichi S. , Ginete Daren R. , Karney Monika MA. , Usufzy Pashtana , Castellanos Maria I. , Duhart Juan Carlos , Harrison Dustin J. , Socea Jillian N. , Karabachev Alexander D. , Hensley Christopher T. , Howerton Amber J. , Ojeda‐Daulo Rosa , Immak Joy A. , Wing Helen J.
Published: February 2018

Transcriptional silencing and anti‐silencing mechanisms modulate bacterial physiology and virulence in many human pathogens. In Shigella species, many virulence plasmid genes are silenced by the histone‐like nucleoid structuring protein H‐NS and anti‐silenced by the virulence gene regulator VirB. Despite the key role that these regulatory proteins play in Shigella virulence, their mechanisms of transcriptional control remain poorly understood. Here, we characterize the regulatory elements and their relative spacing requirements needed for the transcriptional silencing and anti‐silencing of icsP, a locus that requires remotely located regulatory elements for both types of transcriptional control. Our findings highlight the flexibility of the regulatory elements' positions with respect to each other, and yet, a molecular roadblock docked between the VirB binding site and the upstream H‐NS binding region abolishes transcriptional anti‐silencing by VirB, providing insight into transcriptional anti‐silencing. Our study also raises the need to re‐evaluate the currently proposed VirB binding site. Models of transcriptional silencing and anti‐silencing at this genetic locus are presented, and the implications for understanding these regulatory mechanisms in bacteria are discussed.
Methionine is required for cAMP‐PKA‐mediated morphogenesis and virulence of Candida albicans
Authors: Schrevens Sanne , Van Zeebroeck Griet , Riedelberger Michael , Tournu Hélène , Kuchler Karl , Van Dijck Patrick
Published: February 2018

Candida albicans is a major human fungal pathogen, causing superficial, as well as life‐threatening invasive infections. Therefore, it has to adequately sense and respond to the host defense by expressing appropriate virulence attributes. The most important virulence factor of C. albicans is the yeast‐to‐hyphae morphogenetic switch, which can be induced by numerous environmental cues, including the amino acid methionine. Here, we show an essential role for methionine permease Mup1 in methionine‐induced morphogenesis, biofilm formation, survival inside macrophages and virulence. Furthermore, we demonstrate that this process requires conversion of methionine into S‐adenosyl methionine (SAM) and its decarboxylation by Spe2. The resulting amino‐propyl group is then used for biosynthesis of polyamines, which have been shown to activate adenylate cyclase. Inhibition of the SPE2 SAM decarboxylase gene strongly impairs methionine‐induced morphogenesis on specific media and significantly delays virulence in the mouse systemic infection model system. Further proof of the connection between methionine uptake and initial metabolism and the cAMP‐PKA pathway was obtained by showing that both Mup1 and Spe2 are required for cAMP production in response to methionine. Our results suggest that amino acid transport and further metabolism are interesting therapeutic targets as inhibitors of this may prevent the morphogenetic switch, thereby preventing virulence.
Role of bi‐weekly serum galactomannan screening for the diagnosis of invasive aspergillosis in haematological cancer patients
Authors: Couchepin Jade , Brunel Anne‐Sophie , Jaton Katia , Meylan Pascal , Bochud Pierre‐Yves , Lamoth Frédéric
Published: February 2018

Invasive aspergillosis (IA) is a life‐threatening infection affecting haematological cancer patients with chemotherapy‐induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi‐weekly serum GM screening has been proposed for a pre‐emptive therapeutic approach of IA in patients not receiving mold‐active prophylaxis. We have analysed all IA cases among patients with haematological malignancies and prolonged chemotherapy‐induced neutropenia (>14 days) in our institution over a 10‐year period (2007‐2017). Serum GM was measured twice weekly and mold‐active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12‐week survival vs 100% among serum GM‐negative patients, P = .006), irrespective of the timing of GM positivity compared to CT. We concluded that bi‐weekly serum GM screening demonstrated limited benefit in this population.
A new method for the rapid characterization of root growth and distribution using digital image correlation
Authors: Bao Tan , Melenka Garrett W. , Ljubotina Megan K. , Carey Jason P. , Cahill James F.
Published: February 2018

Rapidly determining root growth patterns is biologically important and technically challenging. Current methods focus on direct observation of roots and require destructive excavations or time‐consuming root tracing.

We developed a novel methodology based on analyzing soil particle displacement, rather than direct observation of roots. This inferred root growth method uses digital image correlation (DIC) analysis, an established and high‐throughput method used in many engineering and science disciplines.

By applying DIC analyses to repeated images of plants grown in clear window boxes, we produced visually intuitive and quantifiable strain maps, indicating the magnitude and direction of soil movement. From this, we could infer root growth and rapidly quantify root system metrics. Strain measures were closely associated with the spatial distribution of roots and correlated with root length measured using conventional approaches. The method also allowed for the detection of root proliferation in nutrient‐enriched soil patches, indicating its suitability for quantifying biological patterns.

This novel application of DIC in root biology is effective, scalable, low cost, flexible and complementary to existing technologies. This method offers a new tool for answering questions in plant biology and will be particularly useful in studies involving temporal dynamics of root processes.
Distinct domains of the AVRPM3A2/F2 avirulence protein from wheat powdery mildew are involved in immune receptor recognition and putative effector function
Authors: McNally Kaitlin Elyse , Menardo Fabrizio , Lüthi Linda , Praz Coraline Rosalie , Müller Marion Claudia , Kunz Lukas , Ben‐David Roi , Chandrasekhar Kottakota , Dinoor Amos , Cowger Christina , Meyers Emily , Xue Mingfeng , Zeng Fangsong , Gong Shuangjun , Yu Dazhao , Bourras Salim , Keller Beat
Published: February 2018

Recognition of the AVRPM3A2/F2 avirulence protein from powdery mildew by the wheat PM3A/F immune receptor induces a hypersensitive response after co‐expression in Nicotiana benthamiana. The molecular determinants of this interaction and how they shape natural AvrPm3a2/f2 allelic diversity are unknown.

We sequenced the AvrPm3a2/f2 gene in a worldwide collection of 272 mildew isolates. Using the natural polymorphisms of AvrPm3a2/f2 as well as sequence information from related gene family members, we tested 85 single‐residue‐altered AVRPM3A2/F2 variants with PM3A, PM3F and PM3FL456P/Y458H (modified for improved signaling) in Nicotiana benthamiana for effects on recognition.

An intact AvrPm3a2/f2 gene was found in all analyzed isolates and the protein variant recognized by PM3A/F occurred globally at high frequencies. Single‐residue alterations in AVRPM3A2/F2 mostly disrupted, but occasionally enhanced, the recognition response by PM3A, PM3F and PM3FL456P/Y458H. Residues enhancing hypersensitive responses constituted a protein domain separate from both naturally occurring polymorphisms and positively selected residues of the gene family.

These results demonstrate the utility of using gene family sequence diversity to screen residues for their role in recognition. This approach identified a putative interaction surface in AVRPM3A2/F2 not polymorphic in natural alleles. We conclude that molecular mechanisms besides recognition drive AvrPm3a2/f2 diversification.
Barley stripe mosaic virus infection requires PKA‐mediated phosphorylation of γb for suppression of both RNA silencing and the host cell death response
Authors: Zhang Xuan , Dong Kai , Xu Kai , Zhang Kun , Jin Xuejiao , Yang Meng , Zhang Yongliang , Wang Xianbing , Han Chenggui , Yu Jialin , Li Dawei
Published: February 2018

The Barley stripe mosaic virus (BSMV) γb protein is a viral suppressor of RNA silencing (VSR) and symptom determinant. However, it is unclear how post‐translational modification affects the different functions of γb.

Here, we demonstrate that γb is phosphorylated at Ser‐96 by a PKA‐like kinase in vivo and in vitro. Mutant viruses containing a nonphosphorylatable substitution (BSMVS96A or BSMVS96R) exhibited reduced viral accumulation in Nicotiana benthamiana due to transient induction of the cell death response that constrained the virus to necrotic areas. By contrast, a BSMVS96D mutant virus that mimics γb phosphorylation spread similarly to the wild‐type virus.

Furthermore, the S96A mutant had reduced local and systemic γb VSR activity due to having compromised its binding activity to 21‐bp dsRNA. However, overexpression of other VSRs in trans or in cis failed to rescue the necrosis induced by BSMVS96A, demonstrating that suppression of cell death by γb phosphorylation is functionally distinct from its RNA silencing suppressor activities.

These results provide new insights into the function of γb phosphorylation in regulating RNA silencing and the BSMV‐induced host cell death response, and contribute to our understanding of how the virus optimizes the balance between viral replication and virus survival in the host plants during virus infection.
A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma
Authors: Mehnert Janice M. , Silk Ann W. , Lee J. H. , Dudek Liesel , Jeong Byeong‐Seon , Li Jiadong , Schenkel Jason M. , Sadimin Evita , Kane Michael , Lin Hongxia , Shih Weichung J. , Zloza Andrew , Chen Suzie , Goydos James S.
Published: February 2018

Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg PO bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1‐positive tumors were enrolled. No objective responses were observed, and accrual was stopped. Stable disease was noted in six (46%) patients, with one patient on study for 42 weeks. Riluzole was well tolerated, with fatigue (62%) as the most common adverse event. Downregulation of MAPK and PI3K/AKT was noted in 33% of paired tumor biopsies. Hypothesis‐generating correlative studies suggested that downregulation of angiogenic markers and increased leukocytes at the active edge of tumor correlate with clinical benefit. Pharmacokinetic analysis showed interpatient variability consistent with prior riluzole studies. Future investigations should interrogate mechanisms of biologic activity and advance the development of agents with improved bioavailability.
How Civil Resistance Succeeds (or Not): Micro‐Dynamics of Unity, Timing, and Escalatory Actions
Authors: Bramsen Isabel
Published: February 2018

The article analyzes the micro‐sociological dynamics of civil resistance in the uprisings in Bahrain and Tunisia (2010‐11). It argues that the Tunisian uprising succeeded because regime repression generated solidarity and unity among diverse groups in society, while the regime increasingly suffered from miscommunication, mistrust, and increasing disobedience. In Bahrain, the movement initially enjoyed a high degree of unity and solidarity mobilizing against regime atrocities, but as the regime allowed protesters to demonstrate with little interference for a month, internal divisions emerged. Whereas Tunisian protesters launched a united escalation at a time of opponent weakness, factions of Bahraini activists escalated at a time of increasing division in the movement and society as a whole which both provoked and enabled a crackdown by the regime. Conclusively, success or failure of an uprising depends on a movement and a regime's ability to maintain unity respectively, as well as the timing of escalatory actions.
Unusual spontaneous porto‐systemic shunt: The importance of diagnosing non‐anatomical porto‐systemic shunts to improve portal flow in pediatric living–related liver transplantation. Case report
Authors: Rubio Juan S. , Rumbo Carolina , Farinelli Pablo A. , Aguirre Nicolás , Ramisch Diego A. , Paladini Hugo , D´Angelo Pablo , Barros Schelotto Pablo , Gondolesi Gabriel E.
Published: February 2018

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of “steal flow syndrome” cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12‐month‐old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post‐operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post‐operative ultrasound identified reversed portal flow, finding a non‐anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re‐operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post‐operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.
Living‐donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow‐up
Authors: Demaret Tanguy , Varma Sharat , Stephenne Xavier , Smets Françoise , Scheers Isabelle , Wanders Ronald , Van Maldergem Lionel , Reding Raymond , Sokal Etienne
Published: February 2018

Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long‐term (17 years post‐LT) and short‐term (9 months post‐LT) follow‐up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long‐term clinical outcomes.
Multimodal treatment including tandem high‐dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas
Authors: Lee Ji Won , Lim Do Hoon , Sung Ki Woong , Lee Hyeong Jin , Yi Eun Sang , Yoo Keon Hee , Koo Hong Hoe , Suh Yeon‐Lim , Shin Hyung Jin
Published: February 2018

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas.
Early Mississippian evaporites of coastal tropical wetlands
Authors: Millward David , Davies Sarah J. , Williamson Fiona , Curtis Rachel , Kearsey Timothy I. , Bennett Carys E. , Marshall John E. A. , Browne Michael A. E.
Published: February 2018

Extensive evaporites in Lower Mississippian successions from palaeoequatorial regions are commonly used as evidence for an arid to semi‐arid palaeoclimate. However, in this article, detailed studies of evaporites and their context refute this interpretation. Detailed sedimentological and petrographical analysis of the Lower Mississippian of northern Britain, is combined with archived log data from more than 40 boreholes across southern Scotland, northern England and Northern Ireland, and published literature from Canada. Two key cores from the Tweed Basin and the northern margin of the Northumberland – Solway Basin contain 178 evaporite intervals and reveal twelve distinct forms of gypsum and anhydrite across seven facies that are associated with planar laminated siltstone and intercalated thin beds of ferroan dolostone. Nodular gypsum and anhydrite, typically in intervals <1 to 2 m thick, are integral components of the succession. Nodular evaporite occurs within about 1 m of a palaeosurface, but most evaporite deposits represent ephemeral brine pans to semi‐permanent hypersaline lakes or salinas on a floodplain that was subjected periodically to storm surges introducing marine waters. Formation of evaporites under a strongly seasonal climate in a coastal wetland is supported by palaeosol types and geochemical proxies, and from palaeobotanical evidence published previously. Although 65% of modern equatorial areas experience a strongly seasonal climatic regime, salinas and sabkhas are a minor component today in comparison with the evidence from these Lower Mississippian successions. This implies that the earliest terrestrial environments were complex and dynamic, providing a diverse range of habitats in which the early tetrapods became terrestrialized and represent a setting that is rarely preserved in the geological record.
Dicer inactivation stimulates limb regeneration ability in Xenopus laevis
Authors: Zhang Mengshi , Yang Li , Yuan Feng , Chen Ying , Lin Gufa
Published: February 2018

The ontogenetic decline of regeneration capacity in the anuran amphibian Xenopus makes it an excellent model for regeneration studies. However, the cause of the regeneration ability decline is not fully understood. MicroRNAs regulate animal development and have been indicated in various regeneration situations. However, little is known about the role of microRNAs during limb regeneration in Xenopus. This study investigates the effect of Dicer, an enzyme responsible for microRNA maturation, on limb development and regeneration in Xenopus. Dicer is expressed in the developing Xenopus limbs and is up‐regulated after limb amputation during both regeneration‐competent and regeneration‐deficient stages of tadpole development. Inactivation of Dicer in early (NF stage 53) tadpole limb buds leads to shorter tibulare/fibulare formation but does not affect limb regeneration. However, in late‐stage, regeneration‐deficient tadpole limbs (NF stage 57), Dicer inactivation restores the regeneration blastema and stimulates limb regeneration. Thus, our results demonstrated that Xenopus limb regeneration can be stimulated by the inactivation of Dicer in nonregenerating tadpoles, indicating that microRNAs present in late‐stage tadpole limbs may be involved in the ontogenetic decline of limb regeneration in Xenopus.
How Distorted Thinking Influence Arab Children Academic Achievement in Israel?
Authors: Gith Emad
Published: February 2018

The purpose of the current study was to examine the relation between the parents Cognitive Distortion and Arab children academic achievements in Israel. 52 fifth grade Arab Children and their parents from Israel were participated. The results indicated that parent's cognitive distortion related negatively to children academic achievements; there is a negative correlation between father's Cognitive distortion and children academic achievements and between mother's Cognitive distortion and children academic achievements. The current research concluded that Parent's Cognitive distortion has a greater relationship with children academic performance. The researchers recommend that appropriate measures, including cognitive mutual counseling program (parents and Children) should be put in place for the Children to achieve both their short-term and long-term educational goals.
Atomic-like high-harmonic generation from two-dimensional materials
Authors: Tancogne-Dejean Nicolas , Rubio Angel
Published: February 2018

Two-dimensional materials offer a unique platform where both bulk and atomic HHG can be investigated.
Survival of spin state in magnetic porphyrins contacted by graphene nanoribbons
Authors: Li Jingcheng , Merino-Díez Nestor , Carbonell-Sanromà Eduard , Vilas-Varela Manuel , de Oteyza Dimas G. , Peña Diego , Corso Martina , Pascual Jose Ignacio
Published: February 2018

A magnetic porphyrin connected to graphene nanoribbons remains magnetic.
Topological transport of sound mediated by spin-redirection geometric phase
Authors: Wang Shubo , Ma Guancong , Chan Che Ting
Published: February 2018

The transport of sound can be affected by the spin-redirection geometric phase associated with sound vortices.
Probing quantum coherence in single-atom electron spin resonance
Authors: Willke Philip , Paul William , Natterer Fabian D. , Yang Kai , Bae Yujeong , Choi Taeyoung , Fernández-Rossier Joaquin , Heinrich Andreas J. , Lutz Christoper P.
Published: February 2018

Phase coherence of single-atom spins on surfaces is investigated in a scanning tunneling microscopy experiment.
Skin-interfaced systems for sweat collection and analytics
Authors: Choi Jungil , Ghaffari Roozbeh , Baker Lindsay B. , Rogers John A.
Published: February 2018

The advances in sweat collection and analytics follow from a convergence of electronics, electrochemistry, and microfluidics.
Late diagnosis: a case of rapidly progressive extranodal NK/T cell lymphoma, nasal type
Authors: Mori Hiroyuki , Ebisawa Kei , Nishimura Mitsushige , Kanazawa Kenji
Published: February 2018

Extranodal natural killer (NK)/T cell lymphoma, nasal type is a condition that has poor prognosis. Accurate diagnosis of lymphoma is made by pathological findings. We report a case of extranodal NK/T cell lymphoma, nasal type affecting the lung and liver and which was difficult to diagnose because of negative biopsy results from multiple sites. A 39-year-old man who had dry cough and fever for 1 month was referred to our hospital. He had pancytopenia and elevated serum levels of lactate dehydrogenase and soluble interleukin-2 receptor. Hepatosplenomegaly and multiple lung nodules were found on imaging study. Specimens of bronchoscopic lung, percutaneous liver, bone marrow and random skin biopsies were all negative. Open lung biopsy was not definitive. Unfortunately, disease progression was rapid and fatal before results of pleural fluid cytology and a second liver biopsy showed extranodal NK/T cell lymphoma, nasal type. This report focused on diagnostic planning for rapidly progressive extranodal NK/T-cell lymphoma, nasal type.
Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study
Authors: Kato Mototsugu , Ito Noriko , Demura Mamiko , Kubo Kimitoshi , Mabe Katsuhiro , Harada Naohiko
Published: February 2018

Introduction

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected.

Methods and analysis

This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration.

Ethics and dissemination

This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017).

Discussion

If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin.

Trial registration number

UMIN000034701.
Assessing factors associated with long-term work disability after cancer in Belgium: a population-based cohort study using competing risks analysis with a 7-year follow-up
Authors: Kiasuwa Mbengi Régine Levo , Nicolaie Alina Mioara , Goetghebeur Els , Otter Renee , Mortelmans Katrien , Missinnne Sarah , Arbyn Marc , Bouland Catherine , de Brouwer Christophe
Published: February 2018

Objectives

The number of workers with cancer has dramatically increasing worldwide. One of the main priorities is to preserve their quality of life and the sustainability of social security systems. We have carried out this study to assess factors associated with the ability to work after cancer. Such insight should help with the planning of rehabilitation needs and tailored programmes.

Participants

We conducted this register-based cohort study using individual data from the Belgian Disability Insurance. Data on 15 543 socially insured Belgian people who entered into the long-term work disability between 2007 and 2011 due to cancer were used.

Primary and secondary outcome measures

We estimated the duration of work disability using Kaplan-Meier and the cause-specific cumulative incidence of ability to work stratified by age, gender, occupational class and year of entering the work disability system for 11 cancer sites using the Fine and Gray model allowing for competing risks.

Results

The overall median time of work disability was 1.59 years (95% CI 1.52 to 1.66), ranging from 0.75 to 4.98 years. By the end of follow-up, more than one-third of the disabled cancer survivors were able to work (35%). While a large proportion of the women were able to work at the end of follow-up, the men who were able to work could do so sooner. Being women, white collar, young and having haematological, male genital or breast cancers were factors with the bestlikelihood to be able to return to work.

Conclusion

Good prognostic factors for the ability to work were youth, woman, white collar and having breast, male genital or haematological cancers. Reviewing our results together with the cancer incidence predictions up to 2025 offers a high value for social security and rehabilitation planning and for ascertaining patients’ perspectives.