bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the melatonin metabolism in Saccharomyces cerevisiae by the bioconversion of related metabolites
Authors: Muñiz‐Calvo Sara , Bisquert Ricardo , Fernández‐Cruz Edwin , García‐Parrilla María C. , Guillamón José M.
Published: January 2019

Melatonin (Mel), originally considered a neurohormone, has been detected in beverages and food‐fermented products in which yeast metabolism is highly important. This indolamine is synthesized from serotonin, with L‐tryptophan being the initial substrate of both. Regarding Mel metabolism, the biosynthetic pathway in mammals consists in four‐step reactions. However, six genes are implicated in the synthesis of Mel in plants, which suggest the presence of many pathways. The aim of this study was to provide new empirical data on the production of Mel and other indole‐related compounds in the yeast Saccharomyces cerevisiae (S. cerevisiae). To this end, we performed the addition of the pathway intermediates in S. cerevisiae cells in different growth stages (exponential and arrested cells) to follow the bioconversion and new indolic compound production from them. The different bioconverted indolic compounds tested (L‐tryptophan, 5‐hydroxytryptophan, tryptamine, serotonin, N‐acetylserotonin, 5‐methoxytryptamine, and Mel) were analyzed by UHPLC‐MS/MS from the extra‐ and intracellular contents. Our results showed that serotonin, in yeast, was prevalently formed via tryptophan decarboxylation, followed by tryptamine hydroxylation as in plants. Mel production from serotonin can be achieved by either N‐acetylation, followed by O‐methylation or O‐methylation, in turn followed by N‐acetylation. Accordingly, the classic pathway of Mel synthesis in vertebrates does not seems prevalent in yeast.
Ramp Up and Ramp Down Dynamics in Digital Services
Authors: Akkermans Henk , Voss Chris , van Oers Roeland
Published: January 2019

Volume ramp ups are notoriously difficult in digital services, where market pressures can lead to ramping up too soon and too rapidly which in turn can lead to the need to ramp down. This paper addresses the challenge of taking innovation to scale in an established firm by enhancing our understanding of the nature of service ramp ups and ramp downs. Digital service ramp ups differ substantially from production ramp ups as the speed is much greater, and problems are visible to customers. However there are similarities between service ramp downs and product recalls and an important contribution is exploring the nature of ramp downs their processes and possible causes. Using an engaged research approach, longitudinal data from three consecutive ramp ups in a European telecom operator were collected. Through analyses of cases, qualitative and quantitative case data, and using a system dynamics model, we identified a set of issues that affect service ramp ups and ramp downs. These include the need to ramp up the service supply chain, biases leading to unrealistic assumptions about scalability and problem‐solving, decision biases in various functions, launching digital services in beta form, a lack of transparency of capacity and lack of learning from previous ramp ups. We show that if these problems are not addressed or resolution is delayed, this can lead to cycles of delay, backlogs and productivity problems and the inevitability of a ramp down. We explore reasons and importance for such delays that lead to service ramp downs.
Disease features of equine coronavirus and enteric salmonellosis are similar in horses
Authors: Manship Arlie J. , Blikslager Anthony T. , Elfenbein Johanna R.
Published: January 2019

Background

Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those ofSalmonellainfections.

Objectives

Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses.

Animals

Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV andSalmonella spp.

Methods

Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive,Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set atP< .05.

Results

Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses withSalmonella. Horses withSalmonellahad significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable.

Conclusions and Clinical Importance

Equine coronavirus andSalmonellainfections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.
Impact of polymorphic transposable elements on linkage disequilibrium along chromosomes
Authors: Choudhury Rimjhim Roy , Rogivue Aude , Gugerli Felix , Parisod Christian
Published: January 2019

Recombination and selection drive the extent of linkage disequilibrium (LD) among loci and therefore affect the reshuffling of adaptive genetic variation. However, it is poorly known to what extent the enrichment of transposable elements (TEs) in recombinationally‐inert regions reflects their inefficient removal by purifying selection and whether the presence of polymorphic TEs can modify the local recombination rate. In this study, we investigate how TEs and recombination interact at fine scale along chromosomes and possibly support linked selection in natural populations. Whole‐genome sequencing data of 304 individuals from nearby alpine populations of Arabis alpina were used to show that the density of polymorphic TEs is specifically correlated with local LD along chromosomes. Consistent with TEs modifying recombination, the characterization of 28 such LD blocks of up to 5.5 Mb in length revealed strong evidence of selective sweeps at a few loci through either site frequency spectrum or haplotype structure. A majority of these blocks were enriched in genes related to ecologically relevant functions such as responses to cold, salt stress or photoperiodism. In particular, the S‐locus (i.e., supergene responsible for strict outcrossing) was identified in a LD block with high levels of polymorphic TEs and evidence of selection. Another such LD block was enriched in cold‐responding genes and presented evidence of adaptive loci related to photoperiodism and flowering being increasingly linked by polymorphic TEs. These results are consistent with the hypothesis that TEs modify recombination landscapes and thus interact with selection in driving blocks of linked adaptive loci in natural populations.
How to analyse plant phenotypic plasticity in response to a changing climate
Authors: Arnold Pieter A. , Kruuk Loeske E. B. , Nicotra Adrienne B.
Published: January 2019

Plant biology is experiencing a renewed interest in the mechanistic underpinnings and evolution of phenotypic plasticity that calls for a re‐evaluation of how we analyse phenotypic responses to a rapidly changing climate. We suggest that dissecting plant plasticity in response to increasing temperature needs an approach that can represent plasticity over multiple environments, and considers both population‐level responses and the variation between genotypes in their response. Here, we outline how a random regression mixed model framework can be applied to plastic traits that show linear or nonlinear responses to temperature. Random regressions provide a powerful and efficient means of characterising plasticity and its variation. Although they have been used widely in other fields, they have only recently been implemented in plant evolutionary ecology. We outline their structure and provide an example tutorial of their implementation.
Osa‐miR398b boosts H2O2 production and rice blast disease‐resistance via multiple superoxide dismutases
Authors: Li Yan , Cao Xiao‐Long , Zhu Yong , Yang Xue‐Mei , Zhang Kai‐Ni , Xiao Zhi‐Yuan , Wang He , Zhao Jing‐Hao , Zhang Ling‐Li , Li Guo‐Bang , Zheng Ya‐Ping , Fan Jing , Wang Jing , Chen Xiao‐Qiong , Wu Xian‐Jun , Zhao Ji‐Qun , Dong Oliver Xiaoou , Chen Xue‐Wei , Chern Mawsheng , Wang Wen‐Ming
Published: January 2019

miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear.

In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b‐regulated rice immunity against the blast fungus Magnaporthe oryzae.

Out of the four target genes of miR398b, mutations in Cu/Zn‐Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX, SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2O2) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity.

Our results demonstrate the roles of different SODs in miR398b‐regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2O2 concentration and thereby improve disease resistance.
Understanding the impact of rural weight loss interventions: A systematic review and meta‐analysis
Authors: Porter Gwenndolyn C. , Laumb Karen , Michaud Tzeyu , Brito Fabiana , Petreca Daniel , Schwieger Gina , Bartee Todd , Yeary Karen H.K. , Estabrooks Paul A.
Published: January 2019

Rural adults have a higher risk of developing obesity than urban adults. Several evidence‐based interventions have targeted rural regions, but their impact, defined as reach (number and representativeness of participants) by effectiveness, has not been examined. The purpose of this review was to determine the impact of rural weight loss interventions and the availability of data across dimensions of the reach, effectiveness, adoption, implementation, and maintenance (RE‐AIM) framework. A systematic review was conducted to identify rural weight loss interventions that targeted adults. RE‐AIM‐related data were abstracted from each article. We performed a meta‐analysis to examine effectiveness. Sixty‐four articles reported on rural weight loss interventions, describing 50 unique interventions. The median number of participants was 107. Median participation rate differed between values reported by the authors (62%) and values computed using a standard method (32%). Two studies reported on sample representativeness; none reported comparisons made between target and actual delivery settings. Median weight loss per participant was 3.64 kg. Meta‐analyses revealed the interventions achieved a significant weight reduction, and longer‐duration interventions resulted in greater weight loss. Rural weight loss interventions appear to be effective in supporting clinically meaningful weight loss but reach and cost outcomes are still difficult to determine.
Real‐world experience with leadless cardiac pacing
Authors: Vaidya Vaibhav R. , Dai Mingyan , Asirvatham Samuel J. , Rea Robert F. , Thome Trena M. , Srivathsan Komandoor , Mulpuru Siva K. , Kusumoto Fred , Venkatachalam Kalpathi L. , Ryan James D. , Friedman Paul A. , Cha Yong‐Mei
Published: January 2019

Background

Leadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers.

Methods

Patients receiving LCP (Micra [Medtronic, Minneapolis, MN, USA] and Nanostim [St. Jude Medical/Abbott Laboratories, Chicago, IL, USA]) between 2014 and 2017 at the Mayo Clinic Heart Rhythm Enterprise practice (Rochester, MN, USA; Jacksonville, FL, USA; and Scottsdale, AZ, USA) were identified. We identified 1:1 age‐ and sex‐matched controls receiving single‐chamber transvenous ventricular pacemakers (TVP). Statistical analyses were performed with JMP 13.0.0 (SAS, Institute Cary, NC, USA).

Results

Ninety patients underwent LCP implantation (73 Micra and 17 Nanostim) with a median follow‐up duration of 62 (interquartile range 28‐169) days. Both groups had 100% successful device implant rates. There were no differences in procedure‐related major (0% vs 1%) or minor complications (8% vs 3%) in the LCP versus TVP groups (P > 0.05). Excluding Nanostim patients, there was a lower rate of device‐related revision or extraction in the Micra versus TVP groups (0% vs 5%, P = 0.028). Device endocarditis was more common in the TVP group (0% vs 3%, P = 0.04). Estimated longevity was greater for the LCP group (median 12.0 vs 10.0 years, P < 0.0001). An increase in severity of tricuspid valve regurgitation (TR) by ≥2 grades occurred in none of the LCP patients, and in 19% of the TVP patients (P = 0.017).

Conclusion

There are no significant differences in procedural complications among patients receiving LCP versus TVP. The Micra group had lower rates of device‐related revision/extraction compared to the TVP group. Patients with leadless pacemaker were less likely to develop endocarditis or worsening TR.
Beyond soil water potential: An expanded view on isohydricity including land–atmosphere interactions and phenology
Authors: Novick Kimberly A. , Konings Alexandra G. , Gentine Pierre
Published: January 2019

Over the past decade, the concept of isohydry or anisohydry, which describes the link between soil water potential (ΨS), leaf water potential (ΨL), and stomatal conductance (gs), has soared in popularity. However, its utility has recently been questioned, and a surprising lack of coordination between the dynamics of ΨL and gs across biomes has been reported. Here, we offer a more expanded view of the isohydricity concept that considers effects of vapour pressure deficit (VPD) and leaf area index (AL) on the apparent sensitivities of ΨL and gs to drought. After validating the model with tree‐ and ecosystem‐scale data, we find that within a site, isohydricity is a strong predictor of limitations to stomatal function, though variation in VPD and leaf area, among other factors, can challenge its diagnosis. Across sites, the theory predicts that the degree of isohydricity is a good predictor of the sensitivity of gs to declining soil water in the absence of confounding effects from other drivers. However, if VPD effects are significant, they alone are sufficient to decouple the dynamics of ΨL and gs entirely. We conclude with a set of practical recommendations for future applications of the isohydricity framework within and across sites.
The role of amino acid metabolism during abiotic stress release
Authors: Batista‐Silva Willian , Heinemann Björn , Rugen Nils , Nunes‐Nesi Adriano , Araújo Wagner L. , Braun Hans‐Peter , Hildebrandt Tatjana M.
Published: January 2019

Plant responses to abiotic stress include various modifications in amino acid metabolism. By using a hydroponic culture system, we systematically investigate modification in amino acid profiles and the proteome of Arabidopsis thaliana leaves during initial recovery from low water potential or high salinity. Both treatments elicited oxidative stress leading to a biphasic stress response during recovery. Degradation of highly abundant proteins such as subunits of photosystems and ribosomes contributed to an accumulation of free amino acids. Catabolic pathways for several low abundant amino acids were induced indicating their usage as an alternative respiratory substrate to compensate for the decreased photosynthesis. Our results demonstrate that rapid detoxification of potentially detrimental amino acids such as Lys is a priority during the initial stress recovery period. The content of Pro, which acts as a compatible osmolyte during stress, was adjusted by balancing its synthesis and catabolism both of which were induced both during and after stress treatments. The production of amino acid derived secondary metabolites was up‐regulated specifically during the recovery period, and our dataset also indicates increased synthesis rates of the precursor amino acids. Overall, our results support a tight relationship between amino acid metabolism and stress responses.
Teachers’ social support, somatic complaints and academic motivation in children and early adolescents
Authors: Sikora Renata Maria
Published: January 2019

The study aim was to find out what is pupils perception of teachers' support and to check if different types of perceived support are connected with the level of somatic symptoms reported by students at school. Additionally the study searched for possible links between students' evaluation of teachers ‘as instructors, guides and caregivers’ and their motivation to attend the class and to study the subject. The results show that students perceived informative teachers' support as the most available. Prevalent somatic symptoms reported by students were those connected with tiredness, distraction, low energy and pain. Teachers' evaluation was positively linked to academic motivation. High level of perceived (1) emotional, (2) informational teachers support and a (3) high ‘mark’ prescribed by student to the teacher via teachers' evaluation were negatively related to somatic symptoms. Due to students composition i.e. children originating from different economic backgrounds, the support perception from this perspective was also analysed. The study results indicate that teachers' support perception by children living in harsh economic conditions depended on the division in which they attend the school.
Transhumance as a driving force of landscape change in the marginal grabens of northern Ethiopia
Authors: Tesfamariam Zbelo , Nyssen Jan , Ghebreyohannes Tesfaalem , Tafere Kelemework , Zenebe Amanuel , Poesen Jean , Deckers Seppe , Van Eetvelde Veerle
Published: January 2019

Transhumance between the Afar lowlands and Tigray escarpments has been a common practice in northern Ethiopia. However, the impact of transhumance on landscape changes in the marginal grabens has not been significantly researched. Hence, this study aims to understand the process of transhumance and the linkages between social and biophysical aspects of the graben landscapes of northern Ethiopia. Google Earth (2010−2016) and Landsat Imageries (1995−2015) were used to analyse the spatio‐temporal landscape changes. Normalized Difference Vegetation Index (NDVI) was applied to measure the change in vegetation cover. Interview and Focus Group Discussions were used to collect perceptions of communities on transhumance and landscape change. The findings reveal that transhumance caused conflicts between the lowlanders and highlanders, which in turn led to displacement of communities. Consequently, the NDVI value of the abandoned settlement increased over time. Conversely, the analysis of Google Earth Imageries and NDVI values show that vegetation cover of the new settlement has decreased. Moreover, the NDVI values of the transhumance areas showed little increase due to the establishments of exclosures in the escarpments. The findings of this study can, therefore, be used to develop targeted interventions aimed at solving transhumance‐induced conflicts, displacement of communities and conservation of natural resources.
The new HLA‐C*05:199 was generated by intralocus recombination involving C*05:01:01:01 and C*16:01:01:01 alleles
Authors: Planelles Dolores , Balas Antonio , Rodríguez‐Cebriá Manuel , Luis‐Hidalgo Mar , Vicario José L.
Published: January 2019

The new HLA allele HLA‐C*05:199 was detected and characterized in a Spanish family.
The fly that tried to save the world: Saproxylic geographies and other‐than‐human ecologies
Authors: Gandy Matthew
Published: January 2019

The discovery of a rare fly in a North London cemetery marks my entry point into a wider reflection on the value and significance of urban biodiversity. Using different indices of ecological endangerment, along with a critical reading of new materialist insights, this paper explores the cultural, political, and scientific significance of saproxylic (rotten wood) invertebrate communities in an urban context. The paper brings the fields of urban ecology and post‐humanism into closer dialogue to illuminate aspects to urban nature that have not been systematically explored within existing analytical frameworks. We consider a series of intersecting worlds, both human and non‐human, as part of a glimpse into saproxylic dimensions to urban nature under a putative transition to a new geo‐environmental epoch.
Income and social communication: The demographics of stock market participation
Authors: Gao Ming , Meng Juanjuan , Zhao Longkai
Published: January 2019

This paper analyses the determinants of stock market participation decisions using officially compiled aggregate stock account opening data in China. Different from the literature that often focuses on one particular dimension, our paper systematically evaluates the relative importance of disposable income, demographic variables, macroeconomic factors, stock market conditions and social communication on both the level and the change of the participation rate. We find that the level of the participation rate is predominately determined by the income factor, followed by various measures of social communication. Social communication plays the most important role in the change of the participation rate, acting as a multiplier to stimulate stock market participation. The effects are more pronounced in high‐income, high‐education, high‐population‐density groups and during the bull market period.
Numerical simulation of the lateral pipe intake: flow and sediment field
Authors: Rahmani Firozjaei Mahmood , Behnamtalab Ehsan , Salehi Neyshabouri Seyed Ali Akbar
Published: January 2019

Hydraulic characteristics of the flow and sediment transport conditions are among the most important issues in design of the lateral intakes in order to minimize the flow loss. In this study, a 3D numerical model has been employed in a parametric study to study the performance of a lateral pipe intake. Observations indicated that the flow was affected by the pipe intake so that the recirculation area was close to the wall of the main channel, the wall of the lateral pipe intake and back of the lateral pipe intake. The pipe intake in vertical direction to the main channel showed the highest performance, although sedimentation behind the pipe intake in this diversion angle was higher. In addition, pipe intake showed a quite acceptable performance for almost 40% intrusion to the main channel width. Relationships for the coefficient of discharge were also developed.
Control of potassium tantalate niobate thin film crystal phase and orientation by atomic layer deposition
Authors: Bickford Justin R. , Sønsteby Henrik Hovde , Strnad Nicholas A. , Zavalij Peter Y. , Hoffman Robert C.
Published: January 2019

Due to its appreciable electro-optical properties, potassium tantalate niobate (KTN) thin films of high quality are expected to enhance the functionality of integrated photonics optical modulators. Unfortunately, they are inherently hard to synthesize. Herein, the authors present atomic layer deposition (ALD) of oriented KTN for the first time. They study the variability in phase content with respect to potassium concentration across a variety of substrates. Films grown with a slight overstoichiometry in potassium show excellent crystal quality of a pure perovskite phase. Highly oriented films were obtained on substrates of a similar lattice constant to bulk potassium tantalate niobate. Nearly stoichiometric potassium contents yield films with similar quality, albeit with trace amounts of pyrochlore. Potassium deficient films consist of an overwhelming amount of pyrochlore. Phase control and orientation control are essential when considering device integration of optical modulators. The authors believe that ALD is an ideal technique to obtain KTN thin films with high growth control.
Researchers object to census privacy measure
Authors: Mervis Jeffrey
Published: January 2019

New approach to preserving confidentiality could harm data quality, critics say.
New Horizons inspects a distant time capsule
Authors: Voosen Paul
Published: January 2019

Kuiper belt "snowman" supports idea that planetary building blocks coalesced from clumps of pebbles.
Seeing the dawn
Authors: Service Robert F.
Published: January 2019

Evidence lines up to offer a new view of how life on our planet may have emerged.
Assembling human brain organoids
Authors: Paşca Sergiu P.
Published: January 2019

Three-dimensional assembloids can be used to study human development and disease
Complete steric exclusion of ions and proton transport through confined monolayer water
Authors: Gopinadhan K. , Hu S. , Esfandiar A. , Lozada-Hidalgo M. , Wang F. C. , Yang Q. , Tyurnina A. V. , Keerthi A. , Radha B. , Geim A. K.
Published: January 2019

Only the water may pass

Removing objects by size to keep only the smallest ones is simple in theory, but it requires a sieve, membrane, or filter with holes small enough to allow only the smallest objects to pass. Gopinadhan
et al.
engineered two-dimensional water channels by removing an atomic plane of atoms from a sandwich made from bulk crystal with a graphene spacer. Water flowed through the channels without resistance, but the channels excluded all ions except for protons because the ion hydration shells could not squeeze through the channels.

Science
, this issue p.
145
Observation of chiral zero mode in inhomogeneous three-dimensional Weyl metamaterials
Authors: Jia Hongwei , Zhang Ruixing , Gao Wenlong , Guo Qinghua , Yang Biao , Hu Jing , Bi Yangang , Xiang Yuanjiang , Liu Chaoxing , Zhang Shuang
Published: January 2019

A photonic Weyl system by design

Theoretically proposed exotic physics is now being explored and realized in condensed matter and photonic systems. Weyl physics arises when the valence band and conduction bands meet at discrete points in the band structure. Jia
et al.
designed and fabricated a photonic metamaterial in which the position of the Weyl points in momentum space could be tuned using a huge artificial magnetic field. Because these points are stable, the ability to design and control such a Weyl system with a robust chiral optical mode could be exploited in future optical information processing applications.

Science
, this issue p.
148
Termites mitigate the effects of drought in tropical rainforest
Authors: Ashton L. A. , Griffiths H. M. , Parr C. L. , Evans T. A. , Didham R. K. , Hasan F. , Teh Y. A. , Tin H. S. , Vairappan C. S. , Eggleton P.
Published: January 2019

Forest termites mitigate the effects of drought

In many tropical regions, where drought is predicted to become more frequent in the coming years, termites are key components of ecosystem function. Ashtonet al.experimentally manipulated termite communities to quantify their role during the 2015–2016 “super El Niño” drought in a Malaysian tropical rainforest. Termite relative abundance more than doubled in control plots during drought, maintaining three major ecosystem processes: decomposition, nutrient heterogeneity, and moisture retention. Seedling mortality increased where termites were suppressed.

Science, this issue p.174
Small-Molecule Inhibitor of FosA Expands Fosfomycin Activity to Multidrug-Resistant Gram-Negative Pathogens
Authors: Tomich Adam D. , Klontz Erik H. , Deredge Daniel , Barnard John P. , McElheny Christi L. , Eshbach Megan L. , Weisz Ora A. , Wintrode Patrick , Doi Yohei , Sundberg Eric J. , Sluis-Cremer Nicolas
Published: January 2019

The spread of multidrug or extensively drug-resistant Gram-negative bacteria is a serious public health issue. There are too few new antibiotics in development to combat the threat of multidrug-resistant infections, and consequently the rate of increasing antibiotic resistance is outpacing the drug development process.
Isoniazid Bactericidal Activity Involves Electron Transport Chain Perturbation
Authors: Zeng Sheng , Soetaert Karine , Ravon Faustine , Vandeput Marie , Bald Dirk , Kauffmann Jean-Michel , Mathys Vanessa , Wattiez Ruddy , Fontaine Véronique
Published: January 2019

Accumulating evidence suggests that the bactericidal activity of some antibiotics may not be directly initiated by target inhibition. The activity of isoniazid (INH), a key first-line bactericidal antituberculosis drug currently known to inhibit mycolic acid synthesis, becomes extremely poor under stress conditions, such as hypoxia and starvation.
Dose-Dependent Synergistic Interactions of Colistin with Rifampin, Meropenem, and Tigecycline against Carbapenem-Resistant Klebsiella pneumoniae Biofilms
Authors: Geladari Anastasia , Simitsopoulou Maria , Antachopoulos Charalampos , Roilides Emmanuel
Published: January 2019

Carbapenem-resistant
Klebsiella pneumoniae
(CR-
Kp
) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampin (RIF), meropenem (MEM), gentamicin (GEN), and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN, or TGC against CR-
Kp
mature biofilms.
In Vitro
Activity of the New β-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with β-Lactams against Mycobacterium abscessus Complex Clinical Isolates
Authors: Kaushik Amit , Ammerman Nicole C. , Lee Jin , Martins Olumide , Kreiswirth Barry N. , Lamichhane Gyanu , Parrish Nicole M. , Nuermberger Eric L.
Published: January 2019

Pulmonary disease due to infection with
Mycobacterium abscessus
complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including β-lactams. MABC organisms express a broad-spectrum β-lactamase that is resistant to traditional β-lactam-based β-lactamase inhibitors but inhibited by a newer non-β-lactam-based β-lactamase inhibitor, avibactam.
Hydropic leiomyoma presenting as a rare condition of pseudo-Meigs syndrome: literature review and a case of a pseudo-Meigs syndrome mimicking ovarian carcinoma with elevated CA125
Authors: Pauls Mehrnoosh , MacKenzie Heather , Ramjeesingh Ravi
Published: January 2019

The clinical scenario of a female patient with a pelvic mass, elevated CA125 tumour marker, pleural effusion and ascites is often associated with malignancy. However, not all cases are malignant. Non-malignant diseases, such as Meigs syndrome and pseudo-Meigs syndrome, must be part of your differential. We present a 56-year-old woman with dyspnoea secondary to a right pleural effusion. After further investigations, a serum cancer antigen-125 was found to be elevated at 437.3 U/mL. CT of her abdomen and pelvis showed a large heterogeneous mass in the pelvis measuring 13.2×9.7×15.1 cm with mild ascites. She was initially thought to have ovarian carcinoma and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with omental biopsy. Pathology from the surgical specimen revealed a hydropic leiomyoma and after removal of pelvic mass her pleural effusion and ascites completely resolved. She was ultimately diagnosed with the rare pseudo-Meigs syndrome.
Tumour in a tumour: a well-differentiated spindle cell sarcoma within a forearm lipoma
Authors: Wadkin James C. R. , Senes Sebastian , Evans Scott , Stevenson Jonathan
Published: January 2019

Lipomas are common, benign, soft tissue masses in adults. Sarcomatous change within a giant lipoma is a very rare event. We present a case of a woman presenting with a forearm lipoma that subsequently developed a central, well-differentiated, spindle-cell sarcoma within the lipoma. This case underlines the importance of identifying red flags for referral of soft tissue tumours.
Recurrent venous thromboembolism after discontinuation of rivaroxaban therapy in a patient with antiphospholipid syndrome
Authors: Yagi Shusuke , Nishiyama Seiichi , Abe Toshio , Sata Masataka
Published: January 2019

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thromboembolic events including venous thromboembolism (VTE) in association with the presence of antiphospholipid antibodies. The standard treatment of VTE historically consists of anticoagulation therapy with warfarin, a vitamin K antagonist. Recently, direct oral anticoagulants, including rivaroxaban have become available for the treatment of VTE. However, the choice of anticoagulant, and the duration of anticoagulation in patients with APS has not been determined yet due to lack of evidence. Here, we report a case of recurrent venous thrombosis after discontinuation of rivaroxaban therapy and avoiding sedentary lifestyle in a patient with APS. We suggest that indefinite anticoagulation therapy might be needed even in low-risk APS cases.
Lifetime economic impact of the burden of childhood stunting attributable to maternal psychosocial risk factors in 137 low/middle-income countries
Authors: Smith Fawzi Mary C , Andrews Kathryn G , Fink Günther , Danaei Goodarz , McCoy Dana Charles , Sudfeld Christopher R , Peet Evan D , Cho Jeanne , Liu Yuanyuan , Finlay Jocelyn E , Ezzati Majid , Kaaya Sylvia F , Fawzi Wafaie W
Published: January 2019

Introduction

The first 1000 days of life is a period of great potential and vulnerability. In particular, physical growth of children can be affected by the lack of access to basic needs as well as psychosocial factors, such as maternal depression. The objectives of the present study are to: (1) quantify the burden of childhood stunting in low/middle-income countries attributable to psychosocial risk factors; and (2) estimate the related lifetime economic costs.

Methods

A comparative risk assessment analysis was performed with data from 137 low/middle-income countries throughout Asia, Latin America and the Caribbean, North Africa and the Middle East, and sub-Saharan Africa. The proportion of stunting prevalence, defined as <−2 SDs from the median height for age according to the WHO Child Growth Standards, and the number of cases attributable to low maternal education, intimate partner violence (IPV), maternal depression and orphanhood were calculated. The joint effect of psychosocial risk factors on stunting was estimated. The economic impact, as reflected in the total future income losses per birth cohort, was examined.

Results

Approximately 7.2 million cases of stunting in low/middle-income countries were attributable to psychosocial factors. The leading risk factor was maternal depression with 3.2 million cases attributable. Maternal depression also demonstrated the greatest economic cost at $14.5 billion, followed by low maternal education ($10.0 billion) and IPV ($8.5 billion). The joint cost of these risk factors was $29.3 billion per birth cohort.

Conclusion

The cost of neglecting these psychosocial risk factors is significant. Improving access to formal secondary school education for girls may offset the risk of maternal depression, IPV and orphanhood. Focusing on maternal depression may play a key role in reducing the burden of stunting. Overall, addressing psychosocial factors among perinatal women can have a significant impact on child growth and well-being in the developing world.
Exercise dependence, eating disorder symptoms and biomarkers of Relative Energy Deficiency in Sports (RED-S) among male endurance athletes
Authors: Torstveit Monica Klungland , Fahrenholtz Ida Lysdahl , Lichtenstein Mia Beck , Stenqvist Thomas Birkedal , Melin Anna Katarina
Published: January 2019

Objectives

To explore associations betweenexercise dependence, eating disorder (ED) symptoms and biomarkers of Relative Energy Deficiency in Sports (RED-S) among male endurance athletes.

Methods

Fifty-three healthy well-trained male cyclists, triathletes and long-distance runners recruited from regional competitive sports clubs were included in this cross-sectional study. The protocol comprised the Exercise Dependence Scale (EXDS), the ED Examination Questionnaire (EDE-Q), measurements of body composition, resting metabolic rate, energy intake and expenditure and blood analysis of hormones and glucose.

Results

Participants with higher EXDS score displayed a more negative energy balance compared with subjects with lower EXDS score (p<0.01). EXDS total score was positively correlated with EDE-Q global score (r=0.41, p<0.05) and the subscale score forrestraint eating(r=0.34, p<0.05) andweight concern(r=0.35, p<0.05). EXDS total score and the subscaleslack of controlandtolerancewere positively correlated with cortisol (r=0.38, p<0.01, r=0.39, p<0.01 and r=0.29, p<0.05, respectively). The EXDS subscaleswithdrawalandtolerancewere negatively correlated with fasting blood glucose (r=−0.31 and r=−0.32, p<0.05, respectively), whileintention effectwas negatively correlated with testosterone:cortisol ratio (r=−0.29, p<0.05) and positively correlated with cortisol:insulin ratio (r=0.33, p<0.05).

Conclusion

In this sample of healthy male athletes, we found associations between higher EXDS scores, ED symptoms and biomarkers of RED-S, such as a more pronounced negative energy balance and higher cortisol levels.
Timely access to care for patients with critical burns in India: a prehospital prospective observational study
Authors: Newberry Jennifer A , Bills Corey B , Pirrotta Elizabeth A , Barry Michele , Ramana Rao Govindaraju Venkata , Mahadevan Swaminatha V , Strehlow Matthew C
Published: January 2019

Background

Low/middle-income countries carry a disproportionate burden of the morbidity and mortality from thermal burns. Nearly 70% of burn deaths worldwide are from thermal burns in India. Delays to medical care are commonplace and an important predictor of outcomes. We sought to understand the role of emergency medical services (EMS) as part of the healthcare infrastructure for thermal burns in India.

Methods

We conducted a prospective observational study of patients using EMS for thermal burns across five Indian states from May to August 2015. Our primary outcome was mortality at 2, 7 and 30 days. We compared observed mortality with expected mortality using the revised Baux score. We used Χ2analysis for categorical variables and Wilcoxon two-sample test for continuous variables. ORs and 95% CIs are reported for all modelled predictor variables.

Results

We enrolled 439 patients. The 30-day follow-up rate was 85.9% (n=377). The median age was 30 years; 56.7% (n=249) lived in poverty; and 65.6% (n=288) were women. EMS transported 94.3% of patients (n=399) to the hospital within 2 hours of their call. Median total body surface area (TBSA) burned was 60% overall, and 80% in non-accidental burns. Sixty-eight per cent of patients had revised Baux scores greater than 80. Overall 30-day mortality was 64.5%, and highest (90.2%) in women with non-accidental burns. Predictors of mortality by multivariate regression were TBSA (OR 7.9), inhalation injury (OR 5.5), intentionality (OR 4.7) and gender (OR 2.2).

Discussion

Although EMS rapidly connects critically burned patients to care in India, mortality remains high, with women disproportionally suffering self-inflicted burns. To combat the burn epidemic in India, efforts must focus on rapid medical care and critical care services, and on a burn prevention strategy that includes mental health and gender-based violence support services.
MicroRNA-92a-1–5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia
Authors: Li Ting , Guo Hanqing , Li Hong , Jiang Yanzhi , Zhuang Kun , Lei Chao , Wu Jian , Zhou Haining , Zhu Ruixue , Zhao Xiaodi , Lu Yuanyuan , Shi Chongkai , Nie Yongzhan , Wu Kaichun , Yuan Zuyi , Fan Dai-Ming , Shi Yongquan
Published: January 2019

Background and aims

Gastric intestinal metaplasia (IM) is common in the gastric epithelium of patients with chronic atrophic gastritis. CDX2 activation in IM is driven by reflux of bile acids and following chronic inflammation. But the mechanism underlying how bile acids activate CDX2 in gastric epithelium has not been fully explored.

Methods

We performed microRNA (miRNA) and messenger RNA (mRNA) profiling using microarray in cells treated with bile acids. Data integration of the miRNA/mRNA profiles with gene ontology (GO) analysis and bioinformatics was performed to detect potential miRNA-mRNA regulatory circuits. Transfection of gastric cancer cell lines with miRNA mimics and inhibitors was used to evaluate their effects on the expression of candidate targets and functions. Immunohistochemistry and in situhybridisation were used to detect the expression of selected miRNAs and their targets in IM tissue microarrays.

Results

We demonstrate a bile acids-triggered pathway involving upregulation of miR-92a-1–5p and suppression of its target FOXD1 in gastric cells. We first found that miR-92a-1–5p was increased in IM tissues and induced by bile acids. Moreover, miR-92a-1–5p was found to activate CDX2 and downstream intestinal markers by targeting FOXD1/FOXJ1 axis and modulating activation of nuclear factor kappa B (NF-κB) pathway. Furthermore, these effects were found to be clinical relevant, as high miR-92a-1–5p levels were correlated with low FOXD1 levels and high CDX2 levels in IM tissues.

Conclusion

These findings suggest a miR-92a-1–5p/FOXD1/NF-κB/CDX2 regulatory axis plays key roles in the generation of IM phenotype from gastric cells. Suppression of miR-92a-1–5p and restoration of FOXD1 may be a preventive approach for gastric IM in patients with bile regurgitation.
Timeline and location of recurrence following successful ablation in Barrett’s oesophagus: an international multicentre study
Authors: Sami Sarmed S , Ravindran Adharsh , Kahn Allon , Snyder Diana , Santiago Jose , Ortiz-Fernandez-Sordo Jacobo , Tan Wei Keith , Dierkhising Ross A , Crook Julia E , Heckman Michael G , Johnson Michele L , Lansing Ramona , Ragunath Krish , di Pietro Massimiliano , Wolfsen Herbert , Ramirez Francisco , Fleischer David , Wang Kenneth K , Leggett Cadman L , Katzka David A , Iyer Prasad G
Published: January 2019

Objective

Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines.

Design

Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies.

Results

594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4–4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI −7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia).

Conclusions

BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.
Estimating the performance of three cardiovascular disease risk scores: the Estonian Biobank cohort study
Authors: Saar Aet , Läll Kristi , Alver Maris , Marandi Toomas , Ainla Tiia , Eha Jaan , Metspalu Andres , Fischer Krista
Published: January 2019

Background

We aim to investigate the predictive ability of PCE (Pooled Cohort Equations), QRISK2 and SCORE (Systematic COronary Risk Estimation) scoring systems for atherosclerotic cardiovascular disease (ASCVD) risk prediction in Estonia, a country with one of the highest ASCVD event rates in Europe.

Methods

Seven-year risk estimates were calculated in risk score–specific subsets of the Estonian Biobank cohort. Calibration was assessed by standardised incidence ratios (SIRs) and discrimination by Harrell’s C-statistics. In addition, a head-to-head comparison of the scores was performed in the intersection of the three score-specific subcohorts.

Results

PCE, QRISK2 and SCORE risk estimates were calculated for 4356, 7191 and 3987 eligible individuals, respectively. During the 7-year follow-up, 220 hard ASCVD events (PCE outcome), 671 ASCVD events (QRISK2 outcome) and 94 ASCVD deaths (SCORE outcome) occurred among the score-specific subsets of the cohort. While PCE (SIR 1.03, 95% CI 0.90 to 1.18) and SCORE (SIR 0.99, 95% CI 0.81 to 1.21) were calibrated well for the cohort, QRISK2 underestimated the risk by 48% (SIR 0.52, 95% CI 0.48 to 0.56). In terms of discrimination, PCE (C-statistic 0.778) was inferior to QRISK2 (C-statistic 0.812) and SCORE (C-statistic 0.865). All three risk scores performed at similar level in the head-to-head comparison.

Conclusion

Of three widely used ASCVD risk scores, PCE and SCORE performed at acceptable level, while QRISK2 underestimated ASCVD risk markedly. These results highlight the need for evaluating the accuracy of ASCVD risk scores prior to use in high-risk populations.
10 most important contemporary challenges in the management of SLE
Authors: Felten Renaud , Sagez Flora , Gavand Pierre-Edouard , Martin Thierry , Korganow Anne-Sophie , Sordet Christelle , Javier Rose-Marie , Soulas-Sprauel Pauline , Rivière Marianne , Scher Florence , Poindron Vincent , Guffroy Aurélien , Arnaud Laurent
Published: January 2019

From a 1-year survival of less than 50% before the discovery of glucocorticoids to over 90% at 10 years in most dedicated centres, the spectrum of SLE has profoundly evolved. Despite this improvement, several major challenges currently remain. The aim of this review is to analyse what are, according to us, the 10 most important contemporary challenges in the management of SLE. Among those are the need to treat to target to favour disease remission (or low disease activity), limit the use of glucocorticoids, derive more comprehensive tools for the evaluation of disease activity, develop more effective drugs (yielding successful trials), dissect the heterogeneity of the disease both at the molecular and genetic levels, identify relevant biomarkers for individualised treatment, manage fertility and pregnancy, tackle comorbidities such as cardiovascular risk, the prevention of infections and osteoporosis, improve the network of care (from the patients’ perspective), and favour a holistic approach (integrating fatigue, adherence to treatment, physical activity). Altogether, these 10 contemporary challenges in SLE may be considered as a roadmap for those involved in the daily care of patients with SLE, as well as for researchers who may wish to contribute to an improved management of this rare and complex disease.