bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid screening of in cellulo grown protein crystals via a small-angle X-ray scattering/X-ray powder diffraction synergistic approach
Authors: Lahey-Rudolph Janine Mia , Schönherr Robert , Jeffries Cy M. , Blanchet Clément E. , Boger Juliane , Ferreira Ramos Ana Sofia , Riekehr Winnie Maria , Triandafillidis Dimitris-Panagiotis , Valmas Alexandros , Margiolaki Irene , Svergun Dmitri , Redecke Lars
Published: September 2020

Crystallization of recombinant proteins in living cells is an exciting new approach for structural biology that provides an alternative to the time-consuming optimization of protein purification and extensive crystal screening steps. Exploiting the potential of this approach requires a more detailed understanding of the cellular processes involved and versatile screening strategies for crystals in a cell culture. Particularly if the target protein forms crystalline structures of unknown morphology only in a small fraction of cells, their detection by applying standard visualization techniques can be time consuming and difficult owing to the environmental challenges imposed by the living cells. In this study, a high-brilliance and low-background bioSAXS beamline is employed for rapid and sensitive detection of protein microcrystals grown within insect cells. On the basis of the presence of Bragg peaks in the recorded small-angle X-ray scattering profiles, it is possible to assess within seconds whether a cell culture contains microcrystals, even in a small percentage of cells. Since such information cannot be obtained by other established detection methods in this time frame, this screening approach has the potential to overcome one of the bottlenecks of intracellular crystal detection. Moreover, the association of the Bragg peak positions in the scattering curves with the unit-cell composition of the protein crystals raises the possibility of investigating the impact of environmental conditions on the crystal structure of the intracellular protein crystals. This information provides valuable insights helping to further understand the in cellulo crystallization process.
Temperature evolution of Fe–27Ga structure: comparison of in situ X-ray and neutron diffraction studies
Authors: Bobrikov Ivan A. , Samoylova Nataliya Yu. , Sumnikov Sergey V. , Ivanshina Olga Yu. , Korneeva Ekaterina A. , Balagurov Anatoly M. , Golovin Igor S.
Published: September 2020

Comparative in situ X-ray and neutron diffraction studies of the phase transitions in a high magnetostriction Fe–27Ga alloy sample have been performed, with heating up to 850°C and subsequent cooling to room temperature. Different structural information (phase content, phase-transition temperatures, unit-cell behaviour) is obtained for the bulk sample and its surface, and this fact is discussed here in terms of the difference between the scattering properties of X-rays and neutrons. In particular, a gallium-deficient phase with A2-type structure was found on the surface of the sample. The results demonstrate that conventional X-ray diffraction methods are insufficient for precise structural analysis of bulk samples of galfenols and cannot be used alone to build their phase diagrams.
Automated orientation of water molecules in neutron crystallographic structures of proteins
Authors: Eriksson Axl , Caldararu Octav , Ryde Ulf , Oksanen Esko
Published: September 2020

The structure and function of proteins are strongly affected by the surrounding solvent water, for example through hydrogen bonds and the hydrophobic effect. These interactions depend not only on the position, but also on the orientation, of the water molecules around the protein. Therefore, it is often vital to know the detailed orientations of the surrounding ordered water molecules. Such information can be obtained by neutron crystallography. However, it is tedious and time-consuming to determine the correct orientation of every water molecule in a structure (there are typically several hundred of them), which is presently performed by manual evaluation. Here, a method has been developed that reliably automates the orientation of a water molecules in a simple and relatively fast way. Firstly, a quantitative quality measure, the real-space correlation coefficient, was selected, together with a threshold that allows the identification of water molecules that are oriented. Secondly, the refinement procedure was optimized by varying the refinement method and parameters, thus finding settings that yielded the best results in terms of time and performance. It turned out to be favourable to employ only the neutron data and a fixed protein structure when reorienting the water molecules. Thirdly, a method has been developed that identifies and reorients inadequately oriented water molecules systematically and automatically. The method has been tested on three proteins, galectin-3C, rubredoxin and inorganic pyrophosphatase, and it is shown that it yields improved orientations of the water molecules for all three proteins in a shorter time than manual model building. It also led to an increased number of hydrogen bonds involving water molecules for all proteins.
Guiding the student entrepreneur – Considering the emergent adult within the pedagogy–andragogy continuum in entrepreneurship education
Authors: Hägg Gustav , Kurczewska Agnieszka
Published: September 2020

Purpose

The purpose of the paper is to build on current discussions about the need for and role of guidance in learning and teaching, as well as to theoretically develop its specifics to further advance our scholarly understanding of how to structure and enhance entrepreneurship education.

Design/methodology/approach

The paper takes a synthesizing conceptual approach, built on developmental psychology, instructional science, expertise research as well as the pedagogy–andragogy discussion and the role of guidance in contemporary entrepreneurship education research. In addition, a new term, odigogy, is developed.

Findings

Odigogy, from the Greek word odigós (to guide), addresses how to navigate student entrepreneurs in higher education. The term seeks to correspond both to the specifics of entrepreneurship as a subject and the characteristics of students in the classroom who are in a transitional phase between adolescence and adulthood.

Practical implications

The paper contributes to current entrepreneurship education discussions by offering a more balanced terminology positioned between how to teach (pedagogy) and how adults learn (andragogy). The paper provides insights for teachers when developing teaching methods and learning activities in higher education.

Originality/value

By introducing the term odigogy the paper seeks to contribute an enhanced understanding of the entrepreneurial learning process in higher education, which does not match pedagogical assumptions on how to teach children or adolescents, nor andragogical assumptions on how adults learn, or how to engage students in self-directed learning as presented in heutagogy.
Links between influence strategies and satisfaction: reexamination from the dyadic and network perspectives
Authors: Liu Yi , Liu Ting , Li Yuan , Ruan Liyang
Published: September 2020

Purpose

Previous studies have investigated the influence strategy–economic satisfaction links within a pairwise framework. This study aims to reexamine this issue in a network context from both the structural and relational embeddedness perspectives.

Design/methodology/approach

An ego network approach in which the network consists of a focal distributor, other distributors and alternate manufacturers is adopted to measure the distributor’s network. Drawing on data from 124 distributors from China’s tire industry, a hierarchical multiple regression analysis is used to test the hypotheses.

Findings

The empirical results find a positive relationship between a manufacturer’s noncoercive influence strategies and the distributor’s economic satisfaction and an inverse U-shaped relationship between coercive influence strategies and economic satisfaction. It discusses the joint effects of coercive and noncoercive influence strategies and finds that the former mitigate the positive effects of the latter and that the latter flatten the inverse-U shaped effect of the former. Further, when a distributor spans rich structural holes, the effects of coercive and noncoercive influence strategies on economic satisfaction weaken. When a distributor has strong ties with its network members, the effects of noncoercive influence strategies are mitigated, while the effects of coercive influence strategies are enhanced.

Practical implications

This study provides implications for manufacturers, particularly concerning how to properly exert influence strategies to improve distributors’ economic satisfaction. Manufacturers should consider the attributes of the networks in which the distributors are embedded, involving structural holes and tie strength. They should also carefully use the two influence strategies simultaneously.

Originality/value

This study contributes to the influence strategy literature by incorporating a network perspective by empirically examining the different moderating effects of structural holes and tie strength; provides a new and powerful explanation for the effects that coercive influence strategies have on economic satisfaction by testing an inverse U-shaped effect; and examines the effects of the interaction of two strategies.
Fire resistance of corroded high-strength structural concrete
Authors: Sobhan Khaled , Reddy Dronnadula V. , Martinez Fernando
Published: September 2020

Purpose

The exposure of reinforced concrete structures such as high-rise residential buildings, bridges and piers to saline environments, including exposure to de-icing salts, increases their susceptibility to corrosion of the reinforcing steel. The exposure to fire can further deteriorate the structural integrity of corroded concrete structures. This combined effect of corrosion damage and fire exposure is not generally addressed in the structural concrete design codes. The synergistic combination of the effects of corrosion and fire forms the basis of this paper.

Design/methodology/approach

Concrete beam specimens with different strengths were prepared, moist-cured and corroded with impressed current. Later, they were “crack-scored” for corrosion evaluation, after which half were exposed to fire in a gas kiln. The fire damage was evaluated by nondestructive testing using ultrasonic pulse velocity. Next, all specimens were tested for residual flexural strength. They were then autopsied, and the level of corrosion was determined based on mass loss of the reinforcement.

Findings

For corroded specimens, the flexural capacity loss because of fire exposure increases as the compressive strength increases. In general, the higher the crack score, the higher the corresponding mass loss, unless some partial/segmental debonding of the reinforcement occurred. The degree of corrosion increases with decreasing compressive strength. The residual moment capacity, based on analytically determined capacities of uncorroded and nonfire-exposed beams, was significantly lower than those of uncorroded beams exposed to fire.

Originality/value

The combined effects of corrosion and fire on the mechanical properties of structural concrete are relatively unknown, and no guidance is available in the existing design codes to address this issue. Accordingly, the findings of the paper are expected to be valuable to both researchers and design engineers and can be regarded as the initial investigation on this topic.
Functional traits explain trophic allometries of cephalopods
Authors: Murphy Kieran J. , Pecl Gretta T. , Richards Shane A. , Semmens Jayson M. , Revill Andrew T. , Suthers Iain M. , Everett Jason D. , Trebilco Rowan , Blanchard Julia L.
Published: September 2020

Individual body size strongly influences the trophic role of marine organisms and the structure and function of marine ecosystems. Quantifying trophic position–individual body size relationships (trophic allometries) underpins the development of size‐structured ecosystem models to predict abundance and the transfer of energy through ecosystems. Trophic allometries are well studied for fishes but remain relatively unexplored for cephalopods.

Cephalopods are important components of coastal, oceanic and deep‐sea ecosystems, and they play a key role in the transfer of biomass from low trophic positions to higher predators. It is therefore important to resolve cephalopod trophic allometries to accurately represent them within size‐structured ecosystem models.

We assessed the trophic positions of cephalopods in an oceanic pelagic (0–500 m) community (sampled by trawling in a cold‐core eddy in the western Tasman Sea), comprising 22 species from 12 families, using bulk tissue stable isotope analysis and amino acid compound‐specific stable isotope analysis. We assessed whether ontogenetic trophic position shifts were evident at the species‐level and tested for the best predictor of community‐level trophic allometry among body size, taxonomy and functional grouping (informed by fin and mantle morphology).

Individuals in this cephalopod community spanned two trophic positions and fell into three functional groups on an activity level gradient: low, medium and high. The relationship between trophic position and ontogeny varied among species, with the most marked differences evident between species from different functional groups. Activity‐level‐based functional group and individual body size are best explained by cephalopod trophic positions (marginal R2 = 0.43).

Our results suggest that the morphological traits used to infer activity level, such as fin‐to‐mantle length ratio, fin musculature and mantle musculature are strong predictors of cephalopod trophic allometries. Contrary to established theory, not all cephalopods are voracious predators. Low activity level cephalopods have a distinct feeding mode, with low trophic positions and little‐to‐no ontogenetic increases. Given the important role of cephalopods in marine ecosystems, distinct feeding modes could have important consequences for energy pathways and ecosystem structure and function. These findings will facilitate trait‐based and other model estimates of cephalopod abundance in the changing global ocean.
Transcriptomic reprogramming of the oceanic diatom Skeletonema dohrnii under warming ocean and acidification
Authors: Thangaraj Satheeswaran , Sun Jun
Published: September 2020

Under ocean warming and acidification, diatoms use a unique acclimation and adaptation strategy by saving energy and utilizing it for other cellular processes. However, the molecular mechanisms that underlie this reprogramming of energy utilization are currently unknown. Here, we investigate the metabolic reprogramming of the ecologically important diatom Skeletonema dohrnii grown under two different temperature (21°C and 25°C) and pCO2 (400 and 1000 ppm) levels, utilizing global transcriptomic analysis. We find that evolutionary changes in the baseline gene expression, which we termed transcriptional up‐ and downregulation, is the primary mechanism used by diatoms to acclimate to the combined conditions of ocean warming and acidification. This transcriptional regulation shows that under higher temperature and pCO2 conditions, photosynthesis, electron transport and carboxylation were modified with increasing abundances of genes encoding ATP, NADPH and carbon gaining for the carbon‐dioxide‐concentrating mechanisms (CCMs). Our results also indicate that changes in the transcriptional regulation of CCMs led to a decrease in the metabolic cost to save energy by promoting amino acid synthesis and nitrogen assimilation for the active protein processing machinery to adapt to warming and ocean acidification. This study generated unique metabolic insights into diatoms and suggests that future climate change conditions will cause evolutionary changes in oceanic diatoms that will facilitate their acclimation strategy.
Receipt of opioids and patient care experiences among nonsurgical hospitalized adults
Authors: Mazurenko Olena , Blackburn Justin , Bair Matthew J. , Kara Areeba Y. , Harle Christopher A.
Published: September 2020

Objective

To examine the association between receipt of opioids and patient care experiences among nonsurgical hospitalized adults.

Data Sources

A total of 17 691 patient‐level responses to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient care experience survey linked to medical records from nonsurgical hospitalizations in an 11‐hospital health care system in a Midwestern state, years 2011‐2016.

Study Design

We conducted a pooled cross‐sectional study that used propensity score matching analyses and logistic regression to estimate the relationship between patients’ care experience measures (overall and pain‐specific) and their receipt of opioids while hospitalized. In supplementary analyses, we used the same propensity score matching methods to estimate the relationship between patient care experience measures and receipt of opioids in four patient subgroups based on average patient‐reported pain during hospitalization (no pain; mild pain; moderate pain; and severe pain).

Principal Findings

Receipt of opioids was not associated with patient care experience measures in our main analysis. In our supplementary analysis, we found lower ratings for pain control among hospitalizations for patients who reported moderate pain (Marginal Effects = −4.5 percent; P value = .015).

Conclusions

Counter to some previous studies, we observed that receipt of opioids was not associated with patient care experience measures for nonsurgical hospitalized adults. These findings may be due to different pain experiences of adults hospitalized for nonsurgical versus surgical reasons.
Heterogeneous Demand and Supply for an Insurance‐linked Credit Product in Kenya: A Stated Choice Experiment Approach
Authors: Shee Apurba , Turvey Calum G. , Marr Ana
Published: September 2020

We employ a discrete choice experiment to elicit demand and supply side preferences for insurance‐linked credit, a promising market‐based tool for managing agricultural weather risks and providing access to credit for farmers. We estimate preference heterogeneity using primary data from smallholder farmers and managers of lenders/insurers combined with household socio‐economic survey data in Kenya. We analyse the choice data using maximum simulated likelihood and Hierarchical Bayes estimation of a mixed logit model. Although there are some similarities, we find that there is conflicting demand and supply side preferences for credit terms, collateral requirements, and loan use flexibility. We also analyse willingness to buy and willingness to offer for farmers and suppliers, respectively, for the risk premium for different attributes and their levels. Identifying the preferred attributes and levels for both farmers and financial institutions can guide optimal packaging of insurance and credit providing market participation and adoption motivation for insurance‐bundled credit product.
Effect of storage time on physical properties of sonocrystallized all‐purpose shortening
Authors: Lee Juhee , Marsh Melissa , Martini Silvana
Published: September 2020

The purpose of this study was to determine the effect of high‐intensity ultrasound (HIU) on the physical properties of an all‐purpose shortening and to evaluate how these properties changed during storage (48 hr; 4, 12, and 24 weeks) at 5 °C and 25 °C. Samples were crystallized at 30 °C for 60 min with and without the application of HIU (20 kHz; 3.2 mm‐diameter tip, 168 µm amplitude, 10 s). After crystallization, physical properties, such as hardness, elasticity, melting behavior, and solid fat content (SFC), were measured. These properties were also measured during storage. The effect of HIU was significant in changing the SFC, hardness, G′ and G′′, melting enthalpy, and microstructure of the samples. After 60 min of crystallization, the sonicated samples had higher values of SFC, hardness, elasticity, and melting enthalpy than the ones obtained without sonication (P < 0.05). Changes in these physical properties were associated with the microstructure of the samples since sonication generated smaller, more uniformly sized crystals as well as increased the number of crystals. No differences were observed in the G′ of the sonicated samples stored at 25 °C as a function of storage period. The G′ of the nonsonicated samples increased until 12 weeks of storage and was maintained up to 24 weeks, suggesting that sonication speed up the formation of a stable crystalline network. Samples stored at 5 °C showed higher value in hardness, G′ and G′′, and SFC than the ones stored at 25 °C.

Practical Application

High‐intensity ultrasound (HIU) has been widely used as an additional tool to change the crystallization behavior in various lipids; however, the long‐term storage effect of HIU has not been studied before. This research evaluates the effect of HIU on the physical properties of a palm‐based shortening stored up to 24 weeks at two different temperatures (25 and 5 °C). The application of HIU may help increase the stability of lipid during storage.
Contribution of gestational diabetes mellitus heterogeneity and prepregnancy body mass index to large‐for‐gestational‐age infants—A retrospective case‐control study
Authors: Wang Ning , Song Lin , Sun Bo , Peng Yanqi , Fei Sijia , Cui Jiaqi , Mi Yang , Cui Wei
Published: September 2020

Objective

To study the associations between heterogeneity of gestational diabetes mellitus (GDM) subtype/prepregnancy body mass index (pre‐BMI) and large‐for‐gestational‐age (LGA) infants of Chinese women.

Methods

We performed a retrospective case‐control study of 299 women with GDM and 204 women with normal glucose tolerance (NGT), using oral glucose tolerance test‐based indices performed at 24‐25 weeks of gestation. Women with GDM were classified into the following three physiologic subtypes: GDM with a predominant insulin‐secretion defect (GDM‐dysfunction), GDM with a predominant insulin‐sensitivity defect (GDM‐resistance), or GDM with both defects (GDM‐mixed). We then used a binary logistic regression model to evaluate the potential associations of GDM subtypes and pre‐BMI with newborn macrosomia or LGA.

Results

Women with GDM‐resistance had a higher pre‐BMI (P < 0.001), whereas women in the GDM‐dysfunction and GDM‐mixed groups had pre‐BMIs comparable to the NGT group. In the logistic regression model, women in the GDM‐mixed group exhibited an increased risk of bearing newborns with macrosomia and LGA, and women in the GDM‐dysfunction group tended to have newborns with LGA after adjusting for pre‐BMI and other potential confounders. Women who were overweight or obese prepregnancy manifested an increased risk of having newborns with macrosomia and LGA relative to normal‐weight women, regardless of whether values were unadjusted or adjusted for all potential confounders. There was no significant interaction between GDM subtype and pre‐BMI for any of the studied outcomes.

Conclusions

Heterogeneity of GDM (GDM‐dysfunction and GDM‐mixed) and prepregnancy overweight/obesity were independently associated with LGA in Chinese women. There was no significant interaction between GDM subtypes and pre‐BMI for LGA.
Bradyrhizobium sp. strain ORS278 promotes rice growth and its quorum sensing system is required for optimal root colonization
Authors: Cai Wenjie , Ou Fuwen , Staehelin Christian , Dai Weijun
Published: September 2020

Many Gram‐negative bacteria communicate by using homoserine lactones (HSLs) as quorum sensing (QS) signals in a cell density‐dependent manner. In addition to fatty acyl‐HSL (acyl‐HSL) signals, certain strains, most of them associated with plants, produce non‐canonical aryl‐HSLs such as cinnamoyl‐HSL. However, the role of aryl‐HSL in endophytic associations remained elusive. Bradyrhizobium sp. strain ORS278 possesses a LuxI–LuxR type QS system and produces cinnamoyl‐HSL as a QS signal. Here, we report that strain ORS278 promotes growth of domesticated rice (Oryza sativa). QS mutants unable to produce cinnamoyl‐HSL exhibited reduced plant‐growth promoting activity in comparison to the parent strain ORS278. Likewise, the QS mutants were impaired in their ability to colonize rice roots. These findings suggest that genes controlled by cinnamoyl‐HSL play an important role in the association between rice and ORS278. However, biofilm production was not visibly altered in these mutants. In conclusion, our study highlights the importance of aryl‐HSLs in endophytic plant–bacteria interactions.
Patients with both Langerhans cell histiocytosis and Crohn’s disease highlight a common role of interleukin‐23
Authors: Kvedaraite Egle , Lourda Magda , Han HongYa , Tesi Bianca , Mitchell Jenée , Ideström Maja , Mouratidou Natalia , Rassidakis George , von Bahr Greenwood Tatiana , Cohen‐Aubart Fleur , Jädersten Martin , Åkefeldt Selma Olsson , Svensson Mattias , Kannourakis George , Bryceson Yenan T. , Haroche Julien , Henter Jan‐Inge
Published: September 2020

Aim

To present the first case series of patients with Langerhans cell histiocytosis (LCH) also affected by Crohn's disease (CD), both of which are granulomatous diseases, and in LCH investigate the role of interleukin (IL)‐23, which is a well‐described disease mediator in CD.

Methods

A case series of three patients with LCH and CD were described; a cohort of LCH patients (n = 55) as well as controls (n = 55) were analysed for circulating IL‐23 levels; and the relation between the percentage of LCH cells in lesions and circulating IL‐23 levels was analysed in seven LCH patients.

Results

Differential diagnostic challenges for these two granulomatous diseases were highlighted in the case series, and it took up to 3 years to diagnose CD. Elevated IL‐23 levels were found in LCH patients. The amount of lesional LCH cells correlated with the levels of circulating IL‐23.

Conclusion

Both CD and LCH should be considered in patients with inflammatory gastrointestinal involvement. The IL‐23 pathway is a common immunological trait between these two granulomatous diseases.
Deficiency in insulin‐like growth factors signalling in mouse Leydig cells increase conversion of testosterone to estradiol because of feminization
Authors: Radovic Pletikosic Sava M. , Starovlah Isidora M. , Miljkovic Dejan , Bajic Dragana M. , Capo Ivan , Nef Serge , Kostic Tatjana S. , Andric Silvana A.
Published: September 2020

Aim

A growing body of evidence pointed correlation between insulin‐resistance, testosterone level and infertility, but there is scarce information about mechanisms. The aim of this study was to identify the possible mechanism linking the insulin‐resistance with testosterone‐producing‐Leydig‐cells functionality.

Methods

We applied in vivo and in vitro approaches. The in vivo model of functional genomics is represented by INSR/IGF1R‐deficient‐testosterone‐producing Leydig cells obtained from the prepubertal (P21) and adult (P80) male mice with insulin + IGF1‐receptors deletion in steroidogenic cells (Insr/Igf1r‐DKO). The in vitro model of INSR/IGF1R‐deficient‐cell was mimicked by blockade of insulin/IGF1‐receptors on the primary culture of P21 and P80 Leydig cells.

Results

Leydig‐cell‐specific‐insulin‐resistance induce the development of estrogenic characteristics of progenitor Leydig cells in prepubertal mice and mature Leydig cells in adult mice, followed with a dramatic reduction of androgen phenotype. Level of androgens in serum, testes and Leydig cells decrease as a consequence of the dramatic reduction of steroidogenic capacity and activity as well as all functional markers of Leydig cell. Oppositely, the markers for female‐steroidogenic‐cell differentiation and function increase. The physiological significances are the higher level of testosterone‐to‐estradiol‐conversion in double‐knock‐out‐mice of both ages and few spermatozoa in adults. Intriguingly, the transcription of pro‐male sexual differentiation markers Sry/Sox9 increased in P21‐Leydig‐cells, questioning the current view about the antagonistic genetic programs underlying gonadal sex determination.

Conclusion

The results provide new molecular mechanisms leading to the development of the female phenotype in Leydig cells from Insr/Igf1r‐DKO mice and could help to better understand the correlation between insulin resistance, testosterone and male (in)fertility.
Evaluation of the Xpert MTB/RIF test accuracy for diagnosis of tuberculosis in areas with a moderate tuberculosis burden
Authors: Mansoori Noormohamad , Pahlavanzadeh Bagher , Arabmofrad Fateme
Published: September 2020

The Xpert MTB/RIF assay (Xpert) is a molecular assay used for direct detection of Mycobacterium tuberculosis (MTB) in clinical specimens. In this study, we aimed to assess the accuracy of the Xpert assay for the diagnosis of tuberculosis (TB) in TB suspected patients from the northern region of Iran. The obtained results were compared with the culture method. The sputum specimens were examined using the Xpert assay, smear microscopy, and solid culture media as a reference diagnostic tool. Among 293 presumptive TB cases, 92 (31.4%) were positive according to the culture method. The Xpert method detected 88 (95.7%) cases that were positive according to the culture method, compared with 78 (84.8%) positive cases according to smear microscopy. The overall sensitivity and specificity of the Xpert method for TB diagnosis were 95.7% and 99%, respectively. Also, the sensitivity and specificity for smear microscopy were 84.8% and 97.5%, respectively. The Xpert assay showed high overall sensitivity and specificity; thus, it can be effectively used for the early and accurate diagnosis of MTB in TB endemic areas. In addition, the agreement between semi‐quantitative results of Xpert and smear microscopy assays could be helpful in evaluating transmission potential in TB patients.
Validation of the Korean version of the Generalized Anxiety Disorder 7 self‐rating Scale
Authors: Lee Seung‐Hoon , Shin Cheolmin , Kim Hyounwook , Jeon Sang Won , Yoon Ho‐Kyoung , Ko Young‐Hoon , Pae Chi‐Un , Han Changsu
Published: September 2020

This study examined the validity and reliability of the Korean version of the Generalized Anxiety Disorder‐7 (GAD‐7) scale. The GAD‐7 was standardized with data from 112 patients at a psychiatric outpatient clinic. The GAD‐7 revealed high internal consistency, good test‐retest reliability, and convergent validity. The ROC analysis resulted in poor sensitivity and specificity for detecting anxiety disorders in a psychiatric setting. The GAD‐7 may not be useful in diagnosing anxiety disorders in a psychiatric setting, even though it appears to be a reliable, efficient, and valid measurement tool for evaluating anxiety symptoms.
Jammed Allies: The Ironclad ROK‐U.S. Alliance and China as a Gray Actor
Authors: Ban Kil Joo
Published: September 2020

What drives alliances to tremble? Even longstanding alliances could be frustrated by the jamming mechanism by a gray actor. When an enemy pretends to take a friendlier posture, a state under alliances seems likely to regard its posture as a window of opportunity towards better relationship and wishfully permanent peace. Too much emphasis on this window prevents a state from recognizing how four characteristics of a gray actor – resourceful, ambiguous, temporal and gradual – could risk throwing even an ironclad alliance into chaos. This analysis sheds light on how the ironclad ROK‐U.S. alliance could be jammed by China as a gray actor. These insights contribute to the alliance literature in international relations by focusing on an exogeneous variable to explain weakening alliance cohesion. These outcomes also encourage policymakers to develop a fine counter‐strategy efforts to offset jamming by a gray actor and even alliance decoupling.
Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre‐COVID‐19 reports
Authors: Goldman Adam , Bomze David , Dankner Rachel , Hod Hanoch , Meirson Tomer , Boursi Ben , Maor Elad
Published: September 2020

Aim

There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID‐19) pandemic. We analysed real‐world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ‐associated cardiovascular adverse events (CVAEs) in pre‐COVID‐19 reports.

Methods

We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014‐9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025).

Results

The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3‐35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3‐6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8‐2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9‐2.7], all IC₀₂₅ > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ‐associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively).

Conclusion

In a real‐world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ‐associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off‐label indication, especially for patients with cardiac disorders.
Is gene panel sequencing more efficient than clinical-based gene sequencing to diagnose autoinflammatory diseases? A randomized study
Authors: Rama M , Mura T , Kone-Paut I , Boursier G , Aouinti S , Touitou I , Sarrabay G
Published: September 2020

The aim of this study was to compare the effectiveness of the gene-panel next-generation sequencing (NGS) strategy versus the clinical-based gene Sanger sequencing for the genetic diagnosis of autoinflammatory diseases (AIDs). Secondary goals were to describe the gene and mutation distribution in AID patients and to evaluate the impact of the genetic report on the patient's medical care and treatment. Patients with AID symptoms were enrolled prospectively and randomized to two arms, NGS (n = 99) (32–55 genes) and Sanger sequencing (n = 197) (one to four genes). Genotypes were classified as ‘consistent/confirmatory’, ‘uncertain significance’ or ‘non-contributory’. The proportion of patients with pathogenic genotypes concordant with the AID phenotype (consistent/confirmatory) was significantly higher with NGS than Sanger sequencing [10 of 99 (10·1%) versus eight of 197 (4·1%)]. MEFV, ADA2 and MVK were the most represented genes with a consistent/confirmed genotype, whereas MEFV, NLRP3, NOD2 and TNFRSF1A were found in the ‘uncertain significance’ genotypes. Six months after the genetic report was sent, 54 of 128 (42·2%) patients had received effective treatment for their symptoms; 13 of 128 (10·2%) had started treatment after the genetic study. For 59 of 128 (46%) patients, the results had an impact on their overall care, independent of sequencing group and diagnostic conclusion. Targeted NGS improved the diagnosis and global care of patients with AIDs.
Defective Bcl-2 expression in memory B cells from common variable immunodeficiency patients
Authors: del Pino Molina L , Torres Canizales J M , Pernía O , Rodríguez Pena R , Ibanez de Caceres I , López Granados E
Published: September 2020

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia and different degrees of B cell compartment alteration. Memory B cell differentiation requires the orchestrated activation of several intracellular signaling pathways that lead to the activation of a number of factors, such as nuclear factor kappa B (NF-κB) which, in turn, promote transcriptional programs required for long-term survival. The aim of this study was to determine if disrupted B cell differentiation, survival and activation in B cells in CVID patients could be related to defects in intracellular signaling pathways. For this purpose, we selected intracellular readouts that reflected the strength of homeostatic signaling pathways in resting cells, as the protein expression levels of the Bcl-2 family which transcription is promoted by NF-κB. We found reduced Bcl-2 protein levels in memory B cells from CVID patients. We further explored the possible alteration of this crucial prosurvival signaling pathway in CVID patients by analysing the expression levels of mRNAs from anti-apoptotic proteins in naive B cells, mimicking T cell-dependent activation in vitro with CD40L and interleukin (IL)-21. BCL-XL mRNA levels were decreased, together with reduced levels of AICDA, after naive B-cell activation in CVID patients. The data suggested a molecular mechanism for this tendency towards apoptosis in B cells from CVID patients. Lower Bcl-2 protein levels in memory B cells could compromise their long-term survival, and a possible less activity of NF-κB in naive B cells, may condition an inabilityto increase BCL-XL mRNA levels, thus not promoting survival in the germinal centers.
Consequences of ignoring dispersal variation in network models for landscape connectivity
Authors: Sullivan Lauren L. , Michalska‐Smith Matthew J. , Sperry Katie P. , Moeller David A. , Shaw Allison K.
Published: September 2020

Habitat loss and fragmentation can negatively influence population persistence and biodiversity, but the effects can be mitigated if species successfully disperse between isolated habitat patches. Network models are the primary tool for quantifying landscape connectivity, yet in practice, an overly simplistic view of species dispersal is applied. These models often ignore individual variation in dispersal ability under the assumption that all individuals move the same fixed distance with equal probability. We developed a modeling approach to address this problem. We incorporated dispersal kernels into network models to determine how individual variation in dispersal alters understanding of landscape‐level connectivity and implemented our approach on a fragmented grassland landscape in Minnesota. Ignoring dispersal variation consistently overestimated a population's robustness to local extinctions and underestimated its robustness to local habitat loss. Furthermore, a simplified view of dispersal underestimated the amount of habitat substructure for small populations but overestimated habitat substructure for large populations. Our results demonstrate that considering biologically realistic dispersal alters understanding of landscape connectivity in ecological theory and conservation practice.
Validation of the Danish Colorectal Cancer Group (DCCG.dk) database – on behalf of the Danish Colorectal Cancer Group
Authors: Klein M. F. , Gögenur I. , Ingeholm P. , Njor S. H. , Iversen L. H. , Emmertsen K. J. ,   the DCCG Validation Group
Published: September 2020

Aim

The aim of this study was to validate the clinical quality database of the Danish Colorectal Cancer Group. The validation is meant to focus on core data regarding staging of the disease, treatment provided, patient‐related factors and key complications.

Method

This was a database validation study assessing the completeness of the database and the accuracy of the data by re‐entering core variables into an online module in a blinded fashion and comparing re‐entered data with the original database data. A sample of 5% of patients from the years 2014–2017 was randomly selected.

Results

The sample of 936 patients was identified and data were re‐entered. The completeness of the data retrieved was a median of 96%, 100% and 99% for preoperative, intra‐operative and postoperative variables, respectively. The overall accuracy was a median of 95%. The least accurate variable was date of diagnosis (50% perfect agreement), with agreement rising to 96% when near matches defined as correct date ± 30 days were included. Intra‐operative variables were of high quality, as were data on surgical complications including anastomotic leakage, where agreement was 97%.

Conclusion

This was the first major validation of the Danish Colorectal Cancer Group's database. Overall, the completeness and quality of data were high, but the validation process also identified weaknesses, which can be crucial for future users to acknowledge and consider.
Investigating the spectrum of dermatologic manifestations in COVID‐19 infection in severely ill patients: A series of four cases
Authors: Occidental Michael , Flaifel Abdallah , Lin Lawrence H. , Guzzetta Melissa , Thomas Kristen , Jour George
Published: September 2020

COVID‐19, an infectious disease caused by the novel coronavirus, was initially identified in Wuhan, China, in December 2019. By March 2020, it was declared a pandemic by the World Health Organization. Although most findings have been reported in the lungs, primarily due to catastrophic respiratory decline, other organs, including the skin, are affected. Recent reports have been published describing the clinical spectrum of COVID‐19‐related lesions. In addition, recent case series have described a subset of these lesions having underlying thrombotic microangiopathy with increased complement activation characterized by increased C4d deposition within the blood vessel walls. Herein, we describe a series of COVID‐19‐related cutaneous manifestations found at autopsy examination and their underlying histopathologic findings. Although the clinical manifestations seen in these lesions vary widely, the underlying etiology of thrombotic microangiopathy remains consistent and reproducible.
Spontaneous left atrial multiseptated intramural dissecting hematoma
Authors: Vadgaonkar Vinayak , Yousif Nooraldaem , Sabde Shriram , Slais Salman , Darwish Abdulla , Tarief Habib , Sulaibikh Leena
Published: September 2020

Our case was initially admitted with chest discomfort and congestive heart failure with a presumptive diagnosis of non‐ST segment elevation myocardial infarction and was later found to have a large left atrial (LA) mass. In addition to a complete echocardiography study, multimodality imaging was utilized to better characterize the LA mass. Despite this, the diagnosis could not be confirmed. It was decided to proceed to cardiac surgery, and surprisingly, this revealed a large LA mass with pockets of fresh blood within the LA. Pathological specimen examination confirmed a diagnosis of thrombus, effectively outruling other atrial neoplasms. Although contrast echocardiography and cardiac magnetic resonance imaging suggested this diagnosis, in the absence of any predisposing factors, the final diagnosis was made at surgery and histopathological examination.
A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft
Authors: Zhang Zheng‐zhi‐peng , Zhang Shao‐zhao , Zhou Hui‐min , Fan Yong‐qiang , Liu Meng‐hui , Zhong Xiang‐bin , Yang Da‐ya , Guo Yue , Zhuang Xiao‐dong , Liao Xin‐xue
Published: September 2020

Background

In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice.

Methods and Results

Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than ‘applicability’. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery.

Conclusions

Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.
The world's southernmost tree and the climate and windscapes of the southernmost forests
Authors: Buma Brian , Holz Andrés , Diaz Iván , Rozzi Ricardo
Published: September 2020

The world's southernmost tree has been documented along with the condition and growth pattern of the world's southernmost forest on Isla Hornos, Chile. The distribution of trees at broad scales is strongly influenced by the abiotic environment and determining the position and condition of tree limits around the world is an important way to monitor global change. This offers an ideal way to test the relationship between the biogeography of individual species and the effects of climate/climate change. The limits of trees, as all ecotones, are also useful communication points – easily understood signposts of ecosystems and their change through time. The southernmost trees in the world exist at soil temperatures that correspond to the low range of global treeline temperatures, with a climate analogous to equatorial treeline despite the high latitude (56° S). However, their fine‐scale distribution is strongly influenced by wind exposure rather than simply aspect and/or elevation, as one would expect if temperature were limiting the range. Recent establishment further south was found from core forest areas, however significant dieback along wind‐exposed edges of the contiguous forest was also noted. In contrast to the wide extension of land where boreal or subarctic forests grow in the Northern Hemisphere, in the Southern Hemisphere Isla Hornos represents a single point embedded in the ocean under much milder climatic conditions. Documented shifts in wind intensity and direction as result of larger‐scale climate change will likely continue to strongly shape the condition of these unique forests.
Elevated levels of IL‐18 associated with schizophrenia and first episode psychosis: A systematic review and meta‐analysis
Authors: Syed Ali Alamdar Shah , He Lin , Shi Yongyong , Mahmood Shahid
Published: September 2020

Aim

To determine whether interleukin 18 (IL‐18) is elevated in the blood of schizophrenia (SCZ) and first episode psychosis patients, as well as investigate whether this potential relationship is causal.

Method

We conducted a systematic review and meta‐analysis of IL‐18 levels in the blood of SCZ patients, comprising of both chronic and first episode psychosis (FEP) cohorts. To investigate causality, we undertook the two‐sample Mendelian randomization (MR) study.

Results

A total of eight studies were included in our meta‐analysis, our results did indeed show an association between elevated levels of IL‐18 and SCZ compared to healthy controls (Z = 3.50, P = .0005). This association remained significant in subsequent subgroup analyses for chronic (Z = 3.15, P = .002) and achieved borderline significance in FEP (Z = 1.93, P = .05) SCZ. Our MR analysis failed to detect any causal relationship between IL‐18 levels and SCZ.

Conclusion

The results of our study demonstrate that even though IL‐18 levels are elevated in SCZ patients, IL‐18 levels do not seem to cause of the disorder itself. Our findings suggest that IL‐18 may have utility as a biomarker of SCZ and aid in research into the early intervention of the disease.