bluuebunny/crossref_metadata_2025 huggingface dataset:
First report of an insilico study of Luciferase inMycobacterium sp. EPa45
Authors: Dasgupta Rishav , Pradhan Arpit Kumar , Ghosh Shyamasree
Published: November 2020

Mycobacterium are a genus of Actinobacteria known to be responsible for several deadly diseases in both humans and animals, including tuberculosis. Luciferase is the primary protein inMycobacteriathat plays a role in bioluminescence. It also plays a role in some bacteria of being a source of energy transference, such as in the case of lumazine proteins. Although studies have been conducted in different luciferase in bacteria, there has been hardly any structural studies on luciferase expressed inMycobacterium sp. EPa45. Therefore, in this paper we have studied luciferase expressed inMycobacterium sp. EPa45by insilico analysis of its structure from its protein sequence. We report the observed differences within luciferase reported from other strains of mycobacterium and pathogenic and non-pathogenic forms of bacteria in terms of their (i) physiochemical characteristics, (ii) protein structure, (iii) multiple sequence alignment and (iv) phylogenetic relationships. We report for the first time the relation of this specific strain of Luciferase in mycobacterium and bacterium at large.

Highlights

Mycobacterium sp. EPa45shows similar characteristics to pathogenic mycobacterium

Analysis of Luciferase sequence and protein qualities provides insight to pathogenicity

The deadly nature of infectious mycobacterium, especially with luciferase sequences similar to Mycobacteriumsp. EPa45, is analyzed
HP1 proteins compact DNA into mechanically and positionally stable phase separated domains
Authors: Keenen Madeline M. , Brown David , Brennan Lucy D. , Renger Roman , Khoo Harrison , Carlson Christopher R. , Huang Bo , Grill Stephan W. , Narlikar Geeta J. , Redding Sy
Published: November 2020

In mammals HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1αacts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog’s DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.
An efficient and accurate frailty model approach for genome-wide survival association analysis controlling for population structure and relatedness in large-scale biobanks
Authors: Dey Rounak , Zhou Wei , Kiiskinen Tuomo , Havulinna Aki , Elliott Amanda , Karjalainen Juha , Kurki Mitja , Qin Ashley ,   FinnGen, Lee Seunggeun , Palotie Aarno , Neale Benjamin , Daly Mark , Lin Xihong
Published: November 2020

With decades of electronic health records linked to genetic data, large biobanks provide unprecedented opportunities for systematically understanding the genetics of the natural history of complex diseases. Genome-wide survival association analysis can identify genetic variants associated with ages of onset, disease progression and lifespan. We developed an efficient and accurate frailty (random effects) model approach for genome-wide survival association analysis of censored time-to-event (TTE) phenotypes in large biobanks by accounting for both population structure and relatedness. Our method utilizes state-of-the-art optimization strategies to reduce the computational cost. The saddlepoint approximation is used to allow for analysis of heavily censored phenotypes (>90%) and low frequency variants (down to minor allele count 20). We demonstrated the performance of our method through extensive simulation studies and analysis of five TTE phenotypes, including lifespan, with heavy censoring rates (90.9% to 99.8%) on ~400,000 UK Biobank participants with white British ancestry and ~180,000 samples in FinnGen, respectively. We further performed genome-wide association analysis for 871 TTE phenotypes in UK Biobank and presented the genome-wide scale phenome-wide association (PheWAS) results with the PheWeb browser.
A eukaryote-wide perspective on the diversity and evolution of the ARF GTPase protein family
Authors: Vargová Romana , Wideman Jeremy G. , Derelle Romain , Klimeš Vladimír , Kahn Richard A. , Dacks Joel B. , Eliáš Marek
Published: November 2020

The evolution of eukaryotic cellular complexity is interwoven with the extensive diversification of many protein families. One key family is the ARF GTPases that act in eukaryote-specific processes, including membrane traffic, tubulin assembly, actin dynamics, and cilia-related functions. Unfortunately, our understanding of the evolution of this family is limited. Sampling an extensive set of available genome and transcriptome sequences, we have assembled a dataset of over 2,000 manually curated ARF family genes from 114 eukaryotic species, including many deeply diverged protist lineages, and carried out comprehensive molecular phylogenetic analyses. These reconstructed as many as 16 ARF family members present in the last eukaryotic common ancestor (LECA), nearly doubling the previously inferred ancient system complexity. Evidence for the wide occurrence and ancestral origin of Arf6, Arl13 and Arl16 is presented for the first time. Moreover, Arl17, Arl18 and SarB, newly described here, are absent from well-studied model organisms and as a result their function(s) remain unknown. Analyses of our dataset revealed a previously unsuspected diversity of membrane association modes and domain architectures within the ARF family. We detail the step-wise expansion of the ARF family in the metazoan lineage, including discovery of several new animal-specific family members. Delving back to its earliest evolution in eukaryotes, the resolved relationship observed between the ARF family paralogs sets boundaries for scenarios of vesicle coat origins during eukaryogenesis. Altogether, our work fundamentally broadens the understanding of the diversity and evolution of a protein family underpinning the structural and functional complexity of the eukaryote cells.

Significance

ARF Family GTPases are crucial regulations of a diversity of cellular compartments and processes and as such the extent of this system in eukaryotes reflects both cellular complexity in modern eukaryotes and its evolution. Strikingly, a comprehensive comparative genomic analysis of the protein family is lacking, leaving its recent and ancient evolution poorly resolved. We performed a comprehensive molecular evolutionary analysis, reconstructing a highly complex ARF family complement in the Last Eukaryotic Common Ancestor, including a number of paralogs never before identified as such, and we find resolved relationships between the paralogs. This work has implications for cellular evolution from eukaryogenesis to cellular complexity in metazoans.
In Vitro and Insilico screening platform for the identification of aldose reductase inhibitors for antidiabetic lead compounds fromAbutilon indicum (L.)
Authors: Lavanya L , Veeraraghavan V. , Prashantha CN , Srihari Renuka
Published: November 2020

Introduction

Type 2 Diabetes Mellitus (T2DM) is a long-term metabolic disorder that primarily characterized by impaired insulin resistance to become hyperglycemia. People suffering from T2DM have a higher risk of developing various diseases but, on top of that, some diabetic drugs are also suspected of increasing the risk in some cases. Aldose reductase is a key target enzyme to catalyze the reduction of glucose to sorbitol and does not readily diffuse across cell membranes and cause retinopathy and neuropathy. The aldolase reductase inhibitors prevent the conversion of glucose to sorbitol and may have the capacity of preventing and / or treating several diabetic complications. It will be expected to be twofold in the subsequent decade due to intensification in the senile population with the number of people affected, thus adding to the liability on medical providers in poor developed countries using herbal medicine to control the diabetes. In recent investigation, the antidiabetic property of phytochemicals extracted from leafs ofAbutilon indicum (L.)is elucidated using animal models.

Materials and Methods

In the current study using aldose reductase enzyme assay inhibitor of Rat lens Aldose reductase were treated withA. indicummethanolic leaf extract at different concentrations (6.25, 12.5, 25, 50, 100, and 200μg/mL). Copper sulphate was used as reference drug and docking studies to predict the screen the best aldose reductase inhibitor.

Results and Discussion

The crude extract exhibited cytotoxicity against rat lens aldose reductase (IC50= 135.8 μg/L vs ref 13.60 μg/L) using In Vitro. The docking is performed with 11 compounds shows Ertugliflozin, 9H-Cycloisolongifolene, 8-oxo and 7-hydroxy cadalene showed a good binding interaction with aldose reductase.

Conclusion

We are concluding that the invitro andin silicoanalysis helps researchers to utilize these compound for aldose reductase inhibitors and further can be used for clinical applications.
Lysing Yeast Cells with Glass Beads for Immunoprecipitation
Authors: DeCaprio James , Kohl Thomas O.
Published: November 2020

Yeast cells display cell walls that must first be broken before the addition of detergents for lysis. This method describes the use of glass beads in combination with a mechanical bead beater to disrupt cell walls of both Saccharomyces cerevisiae or Schizosaccharomyces pombe directly in a nonionic detergent Lysis buffer containing 0.1% Nonidet P-40. Alternatively, this protocol can be applied for the lysis of yeast cells in Lysis buffer without detergent; upon completion of the bead beating, Triton X-100 is added to complete lysis. Yeast cells are cultured and collected while in log phase before being washed once and mixed together with glass beads in a tube. The applied shaking process facilitates disruption of the cell walls, upon which separation of yeast and glass beads is accomplished by forcing lysed cells through a hole created in the bottom of the tube during the centrifugation process. An alternative bead-beating protocol details the use of Lysis Buffer 2, which does not contain detergents and calls for the addition of Triton X-100 after cell lysis in the presence of glass beads. Use of Lysis Buffer 2 without detergent may avoid bubble and foam formation during the bead-beating process that could potentially denature proteins.
Cloning in Plasmid Vectors: Directional Cloning
Authors: Green Michael R. , Sambrook Joseph
Published: November 2020

This protocol describes the standard, old-fashioned but reliable procedure for cloning linear DNA fragments whose ends are incompatible with each other but are compatible with those of the linearized vector.
SARS-CoV-2 epidemic calculation in Italy by SEIR compartmental models
Authors: Battineni Gopi , Chintalapudi Nalini , Amenta Francesco
Published: November 2020

Purpose

After the identification of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Wuhan, China, a pandemic was widely spread worldwide. In Italy, about 240,000 people were infected because of this virus including 34,721 deaths until the end of June 2020. To control this new pandemic, epidemiologists recommend the enforcement of serious mitigation measures like country lockdown, contact tracing or testing, social distancing and self-isolation.

Design/methodology/approach

This paper presents the most popular epidemic model of susceptible (S), exposed (E), infected (I) and recovered (R) collectively called SEIR to understand the virus spreading among the Italian population.

Findings

Developed SEIR model explains the infection growth across Italy and presents epidemic rates after and before country lockdown. The results demonstrated that follow-up of strict measures such that country lockdown along with high testing is making Italy practically a pandemic-free country.

Originality/value

These models largely help to estimate and understand how an infectious agent spreads in a particular country and how individual factors can affect the dynamics. Further studies like classical SEIR modeling can improve the quality of data and implementation of this modeling could represent a novelty of epidemic models.
Food waste measurement toward a fair, healthy and environmental-friendly food system: a critical review
Authors: Amicarelli Vera , Bux Christian
Published: November 2020

Purpose

Given the importance of food waste in the economic, social, health and environmental dimensions, the purpose of this work is to detect, through a systematic and configurative literature review on food-waste-measurement methodologies, the global approaches, characteristics, limitations, opportunities and results applied within the literature. The analysis of these papers provides useful information about how far we are from international action plans and, therefore, how we need to direct programs and policies to measure and reduce food waste and ensure food security and food safety.

Design/methodology/approach

The authors have conducted a systematic, configurative literature review on food waste measurement methodologies applied only within empirical studies published in academic peer-reviewed scientific journals. Based on the Commission Delegated Decision (EU) 2019/1597 of May 3, 2019 (OJEU, 2019) regarding common methodologies and minimum quality requirements for the homogeneous assessment of food waste quantities and composition, the authors investigated the issue on Web of Science Core Collection (WoS) from June 2000 to June 2020. The authors researched keywords within article titles, abstracts and author keywords by utilizing 34 different research strings.

Findings

The proposed review particularly refers to following topics: measurement methodologies applied according to the Commission Delegated Decision (EU) 2019/1597; editorial placement and publication timeline; geographical area; food supply-chain stage and publication journals; and the main features, limitations, opportunities and results for each measurement methodology as presented by authors. Among the first 48,000 results, only 58 academic articles are perfectly in line with the aim of the review, highlighting the lack of standardized methodologies, the limits of those proposed and the deficiency of comparable results to achieve sustainable international goals.

Originality/value

The proposed review is one of the few concerning food waste measurement methodologies. Food waste measurement is essential to rebalance the actual inadequate food system and to switch it toward a fair, healthy and environmentally friendly one, thereby (1) managing the human nutrition system paradox of hungry, undernourished and over-weight people; (2) reducing food insecurity; (3) ensuring each living being's access to healthy, nutritious and sustainable food; and (4) reducing environmental impacts (neutral or positive impact) and the loss of biodiversity and mitigating climate change.
Does political risk lower bilateral trade flow? A gravity panel framework for Thailand vis-à-vis her trading partners
Authors: Goswami Gour Gobinda , Panthamit Nisit
Published: November 2020

Purpose

Political risk factors play a pivotal role in determining the bilateral trade flow of Asian countries in general and the Association for Southeast Asian Nations (ASEAN) countries in particular. The main purpose of this research paper is to examine the impact of disaggregated political risk in lowering the bilateral trade flow of Thailand, a prominent member of ASEAN, vis-à-vis her 132 trading partners.

Design/methodology/approach

Using panel data of Thailand with her partner countries for the period 1984–2015, this paper uses four different panel specifications named pooled ordinary least squares and random effects estimations (estimated generalized least squares estimation) of three types by controlling for cross-sectional heteroscedasticity, time-wise heteroscedasticity and contemporaneous correlation.

Findings

Holding other gravity-based determinants constant, for one unit increase in the ranking of indicator of military in politics at home and abroad, trade flow decreases by 5–9% of the total trade flow of Thailand per year. For other types of political risks like government instability at home and abroad, difficulties in investment profile at home and abroad and internal and external conflict at home and abroad, the decrease is also substantial and most statistically significant. The magnitude of loss due to the military channel at home and abroad can amount to US$9.38–US$16.88 bn per year for Thailand, after controlling for other gravity variables.

Research limitations/implications

The reasons for risk originating from different political channels could be explored at the regional or global level to understand their global and local dimensions.

Practical implications

Policymakers should attempt to resolve the political risks at home and abroad in an amicable manner, through dialogue, so that bilateral trade flow is not inhibited.

Social implications

By taking economic reforms only, the trading problem cannot be resolved until and unless Thailand involves her society, politics and administrative mechanisms in a conducive manner to facilitate her trade. A dialogue among bureaucracy, political authority and military is beneficial in mitigating political risks.

Originality/value

The paper is unique in the sense that it makes a solid attempt to identify the potential channels of disaggregated political risk in affecting trade flow negatively, in a gravity framework, by controlling for different kinds of error structure.
Do banks accumulate a higher level of intellectual capital? Evidence from an emerging market
Authors: Tran Ngoc Phu , Vo Duc Hong
Published: November 2020

Purpose

In developed countries, banks are perceived to accumulate a higher level of intellectual capital than firms in other sectors. However, this perception has not been considered or tested in the context of an emerging market such as Vietnam, which has one of the most dynamic economies in the Asian region. This study estimates and compares the level of accumulation of intellectual capital and its four components by financial and nonfinancial firms in Vietnam. Furthermore, this study examines the relationship between intellectual capital and its components and the performance of financial and nonfinancial firms.

Design/methodology/approach

This study uses data collected from the annual reports of 75 financial and 75 nonfinancial firms in Vietnam from 2011 to 2018. A modified value-added intellectual coefficient model is adopted to measure the level of intellectual capital at firms. Various aspects of intellectual capital are considered, including the efficiency of human capital, structural capital, capital employed and relational capital. In addition, the generalized method of moments is used to ensure the robustness of the findings.

Findings

Findings in this study indicate that financial firms in Vietnam have accumulated a higher level of intellectual capital than nonfinancial firms. In addition, intellectual capital contributes positively to financial firms' performance. Three components of intellectual capital – structural capital efficiency, capital employed efficiency and relational capital efficiency – positively affect performance by financial firms.

Research limitations/implications

This study is limited to financial and nonfinancial firms in Vietnam. Empirical studies in the future should incorporate the efficiency aspects of these types of firms because different industries might have different characteristics, in particular, their current efficiency level, which might cause differences in relation to the accumulation of intellectual capital.

Practical implications

The findings of this study provide valuable evidence and implications for executives and policymakers in creating, managing and enhancing intellectual capital within the Vietnamese context, in particular in the financial sector.

Originality/value

To the best of our knowledge, this is the first empirical study conducted in the context of Vietnam, with the following two objectives: (1) to measure and compare the level of accumulation of intellectual capital by financial and nonfinancial firms in Vietnam; and (2) to examine the contribution of intellectual capital and its components to the performance by financial and nonfinancial firms in Vietnam.
Sympatric pairings of dryland grass populations, mycorrhizal fungi and associated soil biota enhance mutualism and ameliorate drought stress
Authors: Remke Michael J. , Johnson Nancy C. , Wright Jeffrey , Williamson Matthew , Bowker Matthew A.
Published: November 2020

There is evidence that the distribution of ecotypes of plants and their symbiotic arbuscular mycorrhizal (AM) fungi and other associated soil biota may be structured by the availability of essential soil nutrients; and that locally adapted partnerships most successfully acquire limiting nutrients. This study tests the hypotheses that plant genotypes are adapted to the water availability of their local environment, and this adaptation involves associations with local soil biota, including AM fungi.

We grew semi‐arid Bouteloua gracilis ecotypes from relatively wet and dry sites, with either sympatric or allopatric soil inoculum under moderate and extreme soil drying treatments to examine (a) how varying degrees of water limitation influence grass responses to soil biota and (b) the relationship between AM fungal structures and the responses.

Under extreme soil drying, the dry site ecotype tended to perform better than the wet site ecotype. Both ecotypes performed best in either drying treatment when inoculated with their sympatric soil biota. Sympatric pairings produced more AM fungal hyphae, arbuscules and dark septate fungi. Extreme soil drying tended to accentuate these apparent benefits of sympatry to both plants and fungal symbionts, relative to the moderate drying treatment.

Our findings support the hypothesis that AM symbioses help Bouteloua gracilis ecotypes adapt to local water availability. This conclusion is based on the observations that as water became increasingly limited, sympatric partnerships produced more AM fungal hyphae and arbuscules and fewer vesicles. The abundances of hyphae and arbuscules were positively correlated with plant growth, suggesting that in sympatric pairs of plants and AM fungi, allocation to fungal structures is optimized to maximize benefits and minimize the costs of the symbioses. This provides strong evidence that co‐adaptation among plants and their associated AM fungi can ameliorate drought stress.

Synthesis. Our study documents the role of locally adapted soil borne plant symbionts in ameliorating water stress. We found a relationship between AM fungal structures in roots and plant performance. Generally, plants and fungi from the same site resulted in more positive effects on plant growth.
Getting the measure of the biodiversity crisis in Mediterranean coastal habitats
Authors: Sperandii Marta Gaia , Barták Vojtěch , Carboni Marta , Acosta Alicia Teresa Rosario
Published: November 2020

Assessing temporal changes in plant communities is a core aim of temporal ecology and a shared priority of global conservation agendas which is particularly urgent in threatened ecosystems. Mediterranean coastal dunes harbour some of the most threatened habitats in Europe. Yet, surprisingly, studies capturing the recent temporal dynamics of biodiversity in these systems by accounting for multiple diversity facets and different aspects of community structure are missing.

Here, using data from a resurveying study, we provide a first comprehensive, habitat‐based, multi‐faceted assessment of recent (10–15 years) temporal changes in threatened Mediterranean coastal dunes. To this aim, we quantified taxonomic and functional changes in plant communities using indices capturing multiple biodiversity features, and we explored trends at both the community level and the species level. We compared observed biodiversity changes across habitats (to look for evidence of generalized biodiversity loss) and across facets (to infer the potential loss of unique functions), and tested their significance using a null model. Overall, we predicted large compositional shifts and biodiversity loss beyond expectations in many communities, although with differences among habitat types.

Our results reveal severe shifts in the taxonomic profile of the communities, mostly driven by a non‐random species loss, and little temporal overlap in functional space, implying large changes in both community structure and ecological strategies of the investigated habitats. This, together with the disappearance of c. 23% of historical plots and with substantial losses in focal species, suggests that intense degradation processes are occurring in coastal dune habitats, particularly on the upper beach and on shifting dunes.

Synthesis. This study provides the first evidence of large, often non‐random, taxonomic and functional changes occurring in Mediterranean coastal dune plant communities in a surprisingly short time‐span. Along with furthering our knowledge of the recent dynamics affecting these endangered ecosystems, our results also pinpoint the types of habitats that are most at risk, helping to direct future conservation efforts and management. Future research should now be directed at more precisely testing potential drivers of these changes.
Development of a Bangla version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI)
Authors: Abdal Syed Jamil , Yesmin Sabrina , Shazzad Md. Nahiduzzamane , Azad Mohammad Abul Kalam , Shahin Md. Abu , Choudhury Minhaj Rahim , Islam Md. Nazrul , Haq Syed Atiqul
Published: November 2020

Aim

Development of a Bangla version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).

Methods

This biphasic observational study performed the translation and adaptation of the questionnaires carried out in 5 steps with pre‐testing in 30 AS patients followed by the psychometric validation of the pre‐final Bangla version utilizing content and construct validity in 115 AS patients. The reliability was examined through internal consistency and test–retest reliability involving 23 AS patients.

Results

After pre‐testing of the pre‐final Bangla version of both indices, the psychometric validation found that the convergent validity of Bangla version of BASDAI showed strong correlation with C‐reactive protein (r = .75) and the Maastricht Ankylosing Spondylitis Enthesitis (r = .64), and moderate correlation with erythrocyte sedimentation rate (r = .49). Again, the Bangla BASFI showed significant correlation with occiput‐to‐wall distance (OWD) (r = .50), mentum‐to‐sternum distance (MSD) (r = .50), chest expansion (CE) (r = −.40), finger‐to‐floor (FFD) (r = .55), number of swollen joints (r = .69), and number of enthesitis (r = .68). The divergent validity demonstrated weak correlations between BASDAI and OWD (r = .43), MSD (r = .34), CE (r = −.44), FFD (r = .47). The divergent validity of BASFI could not be assessed due to lack of a suitable comparing parameter. The instruments revealed acceptable internal consistency as Cronbach's alpha was 0.86 for BASDAI and 0.93 for BASFI. A 7‐day test–retest reliability measured by the intraclass correlation coefficient were 0.80 (CI at 95% = 0.58‐0.90) for BASDAI and 0.83 (CI at 95% = 95% 0.64‐0.92) for BASFI respectively.

Conclusions

Bangla version of BASDAI and BASFI may be useful in disease activity and functional ability assessment in AS patients.
Impact of CYP2D6 activity and cachexia progression on enantiomeric alteration of plasma tramadol and its demethylated metabolites and their relationships with central nervous system symptoms in head and neck cancer patients
Authors: Suzuki Koji , Naito Takafumi , Tanaka Hironari , Shibata Kaito , Yamada Yasuhide , Itoh Kunihiko , Kawakami Junichi
Published: November 2020

This study aimed to evaluate the influence of CYP2D6 activity and cachexia progression on the enantiomeric alteration of plasma tramadol and its demethylated metabolites in head and neck cancer patients. Fifty‐three head and neck cancer patients receiving oral tramadol were enrolled. The plasma concentrations of tramadol, O‐desmethyltramadol (ODT) and N‐desmethyltramadol (NDT) enantiomers were determined. The CYP2D6 activity score (AS) and degree of cachexia progression were assessed according to genotype and the Glasgow Prognostic Score (GPS), respectively. The enantiomeric ratio of NDT was (+)‐form dominant in all patients. CYP2D6 AS had negative correlations with the plasma concentrations of (+)‐NDT and (−)‐NDT. The plasma concentrations of (+)‐tramadol and (+)‐ODT were higher in patients with GPS 1 or 2 than in those with GPS 0. Lower metabolic ratios to NDT enantiomers were observed in patients with GPS 1 or 2. In patients with GPS 1 or 2, the plasma (−)‐tramadol was associated with the incidence of central nervous system symptoms. In conclusion, CYP2D6 AS partially explained the contribution of CYP2D6 activity to plasma tramadol and its demethylated metabolite enantiomers. Additionally, cachexia progression elevated the plasma (+)‐tramadol and (+)‐ODT levels through the reduction of N‐demethylation of (+)‐tramadol.
Efficacy of romiplostim in treatment of thrombocytopenia in children with Wiskott–Aldrich syndrome
Authors: Khoreva Anna , Abramova Irina , Deripapa Elena , Rodina Yulia , Roppelt Anna , Pershin Dmitry , Larin Sergey , Voronin Kirill , Maschan Alexey , Novichkova Galina , Shcherbina Anna
Published: November 2020

Wiskott–Aldrich syndrome (WAS) is a life‐threatening primary immunodeficiency associated with bleeding of variable severity due to thrombocytopenia. Correction of the thrombocytopenia is of paramount importance for most WAS patients. We report a retrospective analysis of the safety and efficacy of romiplostim treatment in reducing thrombocytopenia and bleeding tendency in 67 children (median age 1·3 years) with genetically confirmed WAS, followed in eight months (range, 1–12 months). Complete or partial primary responses regarding platelet counts were observed in 22 (33%) and 18 (27%) subjects, respectively. Yet, even in the non‐responder group, the risk of haemorrhagic events decreased significantly, to 21%, after the first month of treatment. The responses tended to be durable and stable over time, with no significant fluctuations in platelets counts. The results of this retrospective study of a large cohort of WAS patients demonstrates that romiplostim can be used to increase platelet counts and reduce the risks of life‐threatening bleeding in WAS patients awaiting haematopoietic stem cell transplantation or forgoing the procedure for various reasons.
Basophil activation test for Staphylococcus aureus enterotoxins in severe asthmatic patients
Authors: Flora Martina , Perna Francesco , Abbadessa Salvatore , Garziano Federica , Maffucci Rosalba , Maniscalco Mauro , Mollica Mariano , Pelaia Corrado , Tremante Eugenio , Maffei Marianna , Calabrese Cecilia
Published: November 2020

Background

Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST‐1)—can induce both polyclonal and specific IgE responses.

Objective

The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT).

Methods

57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST‐1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1 kU/L and >0.35 kU/L, respectively) were used to assess serum SEsIgE.

Results

36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35 kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations.

Conclusions

The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma.
An X‐linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene
Authors: Tripolszki Kornelia , Sasaki Erina , Hotakainen Ronja , Kassim Abdul Halim , Pereira Catarina , Rolfs Arndt , Bauer Peter , Reardon William , Bertoli‐Avella Aida M.
Published: November 2020

We describe an X‐linked syndrome in 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with intrauterine growth retardation, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. We performed genome sequencing in four individuals and identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. OTUD5 was considered as a candidate gene based on two previous missense variants detected in patients with intellectual disability. In conclusion, we define a syndrome associated with OTUD5 defects and add compelling evidence of genotype–phenotype association. This finding ended the long diagnostic odyssey of this family.
Early technical pancreas failure in Simultaneous Pancreas–Kidney Recipients does not impact renal allograft outcomes
Authors: Das Devika M. , Huskey Janna L. , Harbell Jack W. , Heilman Raymond L. , Singer Andrew L. , Mathur Amit , Neville Matthew R. , Morgan Paige , Reddy Kunam S. , Jadlowiec Caroline C.
Published: November 2020

Early pancreas loss in simultaneous pancreas–kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post‐transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18–1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23–3.06, p = 0.77). One‐ and 2‐year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.
Youth and non‐European ethnicity are associated with increased loss of publicly funded insulin pump access in New Zealand people with type 1 diabetes
Authors: Hennessy Lorelei D. , De Lange Michel , Wiltshire Esko J. , Jefferies Craig , Wheeler Benjamin J.
Published: November 2020

Aims

Continuous subcutaneous insulin infusion (CSII) has been publicly funded in New Zealand for people living with type 1 diabetes since 2012. The aim of the current study was to investigate the loss of access, once obtained, to public‐funded CSII. The frequency and socio‐demographics of access, and loss, to CSII spanning the period 2012 to 2018 were examined.

Methods

Nationally held data collections including the New Zealand Virtual Diabetes Register were used to calculate the overall and subgroup proportions using and ceasing CSII. A logistic regression model was used to estimate odds ratios for pump use for the predictor variables (sex, age group, ethnicity and deprivation index) and to calculate odds ratios for pump cessation for the same demographic factors.

Results

Once CSII access is obtained, approximately 4% per year cease CSII in a subsequent year. This cessation of publicly funded CSII was not distributed equally among the population, showing over‐representation in youth (aged 10–29 years) and non‐Europeans, in particular Māori and Pasifika. Compounding this, it remains less likely for people with diabetes to initially access publicly funded CSII in New Zealand if they are non‐European and more socio‐economically deprived.

Conclusions

In New Zealand, Māori and Pasifika, as well as youth, are over‐represented in the cessation of CSII in comparison with Europeans and all other age groups. These groups are also less likely to gain initial access to public funding. Efforts to understand and reduce these disparities are needed, including review of current public funding access criteria.
Diagnostic utility of mitral annular displacement by speckle tracking echocardiography in predicting significant coronary artery disease in suspected chronic stable angina pectoris
Authors: Sharma Jai Bharat , Deora Surender , Choudhary Rahul , Kaushik Atul
Published: November 2020

Background

More than 50% of patients currently referred for coronary angiography (CAG) with suspected chronic stable angina pectoris (CSAP) shows normal or nonobstructive CAD. Mitral annular displacement (MAD) is a function of global shortening deformation of left ventricle (LV) and mirrors sub‐endocardial ischemia in CAD. The aim of this study was to ascertain if MAD can predict the presence of CAD in patient presenting with suspected CSAP.

Methods

This cross‐sectional study was conducted on patients with suspected CSAP (n = 140) and preserved LV function without apparent wall motion abnormalities during the study period. We excluded patients with prior heart disease (valvular, ischemic), presenting with acute coronary syndrome, arrhythmia, heart failure, and poor imaging. All the patients were subjected to speckle tracking echocardiography (STE) and CAG. Average MAD and normalized MAD were calculated by automated function imaging (AFI), and receiver operating characteristic (ROC) curve was plotted for presence of significant CAD considering CAG as gold standard.

Results

The results showed that both average MAD (4 segment) and normalized MAD were significantly reduced (P = <.001) in patients with significant CAD (n = 81). In ROC analysis, area under curve (AUC) for predicting significant CAD in patients of CSAP was better for normalized MAD (0.88) compared to average MAD (4 segment, 0.85).The optimal cutoff of normalized MAD and average MAD for detection of significant CAD were ≤15.3% (sensitivity 90.1%, specificity 79.7%) and ≤11.19 (sensitivity 84%, specificity 69.5%), respectively. Normalized MAD showed week inverse correlation with SYNTAX score (−0.24, R2 = 0.058) and Hs CRP (−0.23, R2 = 0.057).

Conclusion

MAD is a simple and rapid noninvasive diagnostic tool which accurately predicted the presence of significant CAD in patients with CSAP.
Frailty assessment, hip fracture and long‐term clinical outcomes in older adults
Authors: Pizzonia Monica , Giannotti Chiara , Carmisciano Luca , Signori Alessio , Rosa Gianmarco , Santolini Federico , Caffa Irene , Montecucco Fabrizio , Nencioni Alessio , Monacelli Fiammetta
Published: November 2020

Background

The primary aim of the study was determining the validation of the modified 19‐item Frailty Index (mFI‐19), based on the standard procedure for creating a frailty index scoring in the accumulation deficit theory of Rockwood and comparing it with the gold standard comprehensive geriatric assessment (CGA) in old age patients with hip fracture. As a secondary aim, we compared prognostic accuracies of mFI‐19 and CGA in predicting long‐term mortality after surgery.

Materials and Methods

A total of 364 older patients with hip fractures, each a candidate for surgery, were consecutively enrolled. All were subjected to CGA and mFI‐19 at baseline and time to death (years from hip surgery) were collected prospectively.

Results

Mean patient age was 86.5 (SD: 5.65) years. The most common clinical phenotype (77%) was frail. Both CGA and mFI‐19 performed similarly in predicting long‐term mortality (Harrell's C‐index: 0.66 and 0.68, respectively).

Conclusions

The mFI‐19 was validated, compared to the gold standard CGA, based on a systematic process for creating a frailty index in relation to the accumulation deficit. This is one of few prospective studies addressing long‐term mortality in older adults with hip fractures, invoking a methodologically robust frailty screening assessment.
C‐Reactive Protein: Marker of risk for post‐traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery
Authors: Friend Samantha F. , Nachnani Rahul , Powell Susan B. , Risbrough Victoria B.
Published: November 2020

Increasing evidence indicates that inflammation plays a role in PTSD and stress disorder pathophysiology. PTSD is consistently associated with higher circulating inflammatory protein levels. Rodent models demonstrate that inflammation promotes enduring avoidance and arousal behaviors after severe stressors (e.g., predator exposure and social defeat), suggesting that inflammation may play a mechanistic role in trauma disorders. C‐reactive protein (CRP) is an innate acute phase reactant produced by the liver after acute infection and chronic disease. A growing number of investigations report associations with PTSD diagnosis and elevated peripheral CRP, CRP gene mutations, and CRP gene expression changes in immune signaling pathways. CRP is reasonably established as a potential marker of PTSD and trauma exposure, but if and how it may play a mechanistic role is unclear. In this review, we discuss the current understanding of immune mechanisms in PTSD with a particular focus on the innate immune signaling factor, CRP. We found that although there is consistent evidence of an association of CRP with PTSD symptoms and risk, there is a paucity of data on how CRP might contribute to CNS inflammation in PTSD, and consequently, PTSD symptoms. We discuss potential mechanisms through which CRP could modulate enduring peripheral and CNS stress responses, along with future areas of investigation probing the role of CRP and other innate immune signaling factors in modulating trauma responses. Overall, we found that CRP likely contributes to central inflammation, but how it does so is an area for further study.
Fish and hyperoxia—From cardiorespiratory and biochemical adjustments to aquaculture and ecophysiology implications
Authors: McArley Tristan J. , Sandblom Erik , Herbert Neill A.
Published: November 2020

Hyperoxia occurs when water oxygen (O2) levels exceed normal atmospheric pressure (i.e., >100% air saturation). Fish can experience hyperoxia in shallow environments due to photosynthesis or in aquaculture through O2 supplementation. This review provides a comprehensive synthesis of the effects of hyperoxia on fish, spanning influences on cardiorespiratory function, acid‐base balance, oxidative stress and whole animal performance (e.g., thermal tolerance and growth). Fish hypoventilate in hyperoxia, but arterial and venous blood oxygenation increases in spite of reduced convection. Persistently high levels of blood oxygenation in hyperoxia do not commonly result in reduced blood O2 carrying capacity, but assessments in undisturbed fish are required to clarify this. Hypoventilation also causes the retention of carbon dioxide, hence respiratory acidosis. Another consequence of hyperoxia is increased levels of oxidative stress and concomitant changes to antioxidant defence systems. Despite these changes, however, the bulk of evidence shows no effect of hyperoxia on growth. Hyperoxia does impact the aerobic metabolic rate of fish with either no effect or elevated resting metabolic rate and substantial increases in maximum metabolic rate. There is also evidence that hyperoxia increases aerobic capacity improves cardiac performance and mitigates anaerobic stress during acute warming. Along with improved upper thermal tolerance in some species, these findings collectively suggest that hyperoxia might provide fish a metabolic refuge during acute warming. Since hyperoxia occurs in shallow aquatic habitats, further research establishing the ecophysiological implications of concomitant heat stress and hyperoxia is pertinent, particularly with a changing climate.
Quality of different rice cultivars and factors influencing consumer willingness‐to‐purchase rice
Authors: Charoenthaikij Phantipha , Chaovanalikit Arusa , Uan‐On Tanat , Waimaleongora‐ek Pamarin
Published: November 2020

Physicochemical properties and descriptive profiles of four rice samples including white rice (RD31 and KDML105), brown rice (BKDML) and a brown/red rice mix (BR + HMD) were investigated. Consumer acceptance and factors influencing rice consumption and purchase intent were also determined (n = 112). The unpolished rice samples were more flavourful, harder and lower in retrogradation rate than the polished ones. The RD31 with 36.81% apparent amylose content exhibited the lowest peak viscosity (133.5 RVU) with the highest retrogradation rate (59.7%) resulting in the lowest consumer acceptance. The KDML105 obtained the highest acceptance score (6.9) with the softest texture (23.8 N) and the lowest cooking time (18 min). The preference mapping revealed that consumer acceptance was highly associated with the peak viscosity and vice versa for the amylose content. The factor analysis indicated that the accessibility, eating behaviour, rice variety, preference as well as rice quality and health benefits, respectively, were the factor‐driven consumers’ attitudes towards rice consumption and purchase intention.