bluuebunny/crossref_metadata_2025 huggingface dataset:
A mechanistic pharmacokinetic model with drug and antidrug antibody interplay, and its application for assessing the impact of immunogenicity response on bioequivalence testing
Authors: Liao Kai H. , Udata Chandrasekhar , Yin Donghua , Sewell K. Lea , Kantaridis Constantino , Alvarez Daniel F. , Meng Xu
Published: April 2020

Aims

Single‐dose pharmacokinetic (PK) studies in healthy subjects have been the design of choice for bioequivalence determination for decades. This preference has been recently extended to PK similarity studies of proposed biosimilars. However, PK similarity studies can be complicated by the effect of immunogenicity response on drug disposition. The impact is exacerbated when there is an imbalance in host‐specific immunological characteristics of subjects between the test and reference groups. Such complications remain poorly understood. The purpose of this communication is to show that the impact of immunogenicity response on PK similarity determination can be critical, using adalimumab as an example.

Methods

Data for adalimumab concentrations and immunogenicity response over 10 weeks were obtained from 133 healthy subjects receiving a 40 mg dose of Humira® in a PK similarity study. Also, a population PK model with a mechanistic construct for delineating the interplay between adalimumab disposition and antidrug antibodies response was utilized to estimate via simulation the probability that a PK similarity study would fail in typical study settings.

Results

The simulations showed that the immunogenicity response can have a profound impact on the outcome of PK similarity determination. As such, the probability of failing to achieve the similarity conclusion increased to 51.9%, from 13.8% in the absence of immunogenicity response.

Conclusion

This study provides a model‐based framework for better understanding of how a PK similarity study can be optimally designed and for interpretation of the outcome of PK similarity determination when the drug disposition is affected in the presence of immunogenicity response.
Dentist‐patient relationships and oral health impact in Australian adults
Authors: Song YoungHa , Luzzi Liana , Chrisopoulos Sergio , Brennan David
Published: April 2020

Objectives

Dentist‐patient relationships (DPRs) are a key component in clinical encounters with potential benefits for oral health outcomes. This study aimed to investigate whether better DPR variables are associated with higher oral health‐related quality of life (OHRQoL).

Methods

A total of 12 245 adults aged 18 years or over were randomly sampled from South Australia in 2015‐2016. Data were collected from self‐complete questionnaires and analysed as a cross‐sectional design. The outcome variable was the Oral Health Impact Profile (OHIP‐14). Explanatory DPR variables included trust in dentists, satisfaction with dental care, and dental fear. Covariates comprising oral health behaviours, dental services, demographics, and socioeconomic status were included as potential confounding variables. Bivariate correlation analyses and multivariable linear regression were performed for the associations among explanatory, outcome variables and other covariates.

Results

Response data were analysed from 4220 participants (response rate = 41.9%). Unadjusted mean total scores of DPR variables and OHIP‐14 were associated with most of the study participants' characteristics (P < .05). Bivariate correlations among DPR variables and OHIP‐14 showed a diverse range of coefficients (|r| or |ρ|=0.22‐0.67). Multivariable regression analyses in both individual/clustered block entry and full model indicated that higher satisfaction and less dental fear (B = –0.039 and 0.316, respectively in the full model) were associated with lower OHIP‐14 after adjusting for possible confounders (P < .01).

Conclusions

This study found that favourable DPR variables, mainly greater satisfaction and less dental fear are positively associated with better OHRQoL. Further studies are warranted to investigate the causality and mediation/moderation of DPR variables on oral health outcomes.
Effects of continuous and intermittent aerobic physical training on hormonal and metabolic profile, and body composition in women with polycystic ovary syndrome: A randomized controlled trial
Authors: Ribeiro Victor B. , Kogure Gislaine Satyko , Lopes Iris Palma , Silva Rafael C. , Pedroso Daiana Cristina Chielli , de Melo Anderson S. , de Souza Hugo C. D. , Ferriani Rui Alberto , Miranda Furtado Cristiana Libardi , dos Reis Rosana Maria
Published: April 2020

Objective

To evaluate the effects of continuous (CA) and intermittent (IA) aerobic training on hormonal and metabolic parameters and body composition of women with polycystic ovary syndrome (PCOS).

Design

Prospective, interventional, randomized study.

Methods

Randomized controlled training (RCT) with sample allocation and stratification into three groups: CAT (n = 28) and IAT (n = 29) training and no training [control (CG), n = 30]. Before and after 16 weeks of intervention (CAT or IAT) or observation (CG), hormonal and metabolic parameters, body composition and anthropometric indices were evaluated. Aerobic physical training on a treadmill consisted of 30‐ to 50‐minute sessions with intensities ranging from 60% to 90% of the maximum heart rate.

Results

In the CA group, there was reduction in waist circumference (WC) (P = .045), hip circumference (P = .032), cholesterol (P ≤ .001), low‐density lipoprotein (P = .030) and testosterone (P ≤ .001). In the IAT group, there was a reduction in WC (P = .014), waist‐to‐hip ratio (P = .012), testosterone (P = .019) and the free androgen index (FAI) (P = .037). The CG showed increases in WC (P = .049), total body mass (P = .015), body fat percentage (P = .034), total mass of the arms (P ≤ .001), trunk fat percentage (P = .033), leg fat percentage (P = .021) and total gynoid mass (P = .011).

Conclusion

CAT and IAT training reduced anthropometric indices and hyperandrogenism in PCOS, whereas only IAT training reduced the FAI. Furthermore, only CAT training improved the lipid profile.
PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly
Authors: Khan Amjad , Alaamery Manal , Massadeh Salam , Obaid Abdulrahman , Kashgari Amna A. , Walsh Christopher A. , Eyaid Wafaa
Published: April 2020

Primary microcephaly (PM) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci identified to date. We report a consanguineous family with PM, intellectual disability and short stature. Using whole exome sequencing, we identified a homozygous frameshift variant in programmed cell death 6 interacting protein (PDCD6IP, c.154_158dup; p.Val54Profs*18). This gene, PDCD6IP, plays an important role in the endosomal sorting complexes required for transport (ESCRT) pathway in the abscission stage of cytokinesis and apoptosis, and is required for normal brain development in mice. The clinical features observed in our patient were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. This study provides evidence that clinical manifestations of PDCD6IP mutations as seen in our patients with PM and ID may be a novel cause for neurodevelopmental disorders.
Using ecosystem‐services assessments to determine trade‐offs in ecosystem‐based management of marine mammals
Authors: Riisager‐Simonsen Christian , Rendon Olivia , Galatius Anders , Olsen Morten Tange , Beaumont Nicola
Published: April 2020

The goal of ecosystem‐based management (EBM) is to support a sustainable and holistic multisectored management approach, and is recognized in a number of international policy frameworks. However, it remains unknown how these goals should be linked to assessments and management plans for marine fauna, such as mammals and fish stocks. It appears particularly challenging to carry out trade‐off analyses of various ocean uses without a framework that integrates knowledge of environmental, social, and economic benefits derived from nonstationary marine fauna. We argue this gap can be filled by applying a version of the ecosystem‐service approach at the population level of marine fauna. To advance this idea, we used marine mammals as a case study to demonstrate what indicators could operationalize relevant assessments and deliver an evidence base for the presence of ecosystem services and disservices derived from marine mammals. We found indicators covering common ecosystem service categories feasible to apply; examples of indicator data are already available in the literature for several populations. We encourage further exploration of this approach for application to marina fauna and biodiversity management, with the caveat that conceptual tensions related to the use of the ecosystem service concept itself needs to be addressed to ensure acceptance by relevant stakeholders.
“Elasto‐lung point”: A new tool for the sonographic confirmation of pneumothorax
Authors: Bandelli Gian Piero , Levi Guido , Quadri Federico , Marchetti Gian Pietro
Published: April 2020

Introduction

Standard ultrasound gives the operator a dynamic morphology of the investigated anatomy, whereas ultrasound elastography (USE) provides quantitative and qualitative information about the elastic properties of the tissues.

Objectives

We designed a single‐arm prospective study in order to investigate the feasibility of USE in the diagnosis of pneumothorax if a lung point sign is present.

Methods

Thirty patients were enrolled in this protocol, from January 2017 to December 2018 at the Pneumology Department of the Azienda Socio‐Sanitaria Territoriale Spedali Civili (Brescia, Italy). Patients who were suspected of having pneumothorax were previously evaluated with standard ultrasonography, and then, in the presence of lung point, we performed strain elastography. All patients were evaluated in supine and sitting positions with a linear probe (7.5 MHz). USE enhanced the air‐tissue interface dividing the normal parenchyma from the air column of pneumothorax with a sharp line. We called this sign “elasto‐lung point.”

Results and conclusion

The “elasto‐lung point” was able to confirm the diagnosis of pneumothorax in every investigated patient. USE is a simple, reproducible and inexpensive technique that can contribute to the diagnosis of pneumothorax, such as the classic “stratosphere” or “Bar Code” sign in M‐mode. No false negative cases were observed.
Effect of infrared and red monochromatic light on equine wound healing
Authors: Michanek Peter , Toth Tamás , Bergström Evelina , Treffenberg‐Pettersson Helena , Bergh Anna
Published: April 2020

Background

Light‐emitting diodes (LEDs) are commonly used for treating a variety of disorders in horses, including wounds. Despite its claim to shorten healing times, there is a lack of scientific documentation regarding its effects.

Objectives

To investigate if treatment with pulsating visible red light (λ ≈ 637 nm) and near‐infrared (NIR) light (λ ≈ 956 nm) affects wound healing.

Study design

Randomised blinded controlled experimental study.

Methods

A circular skin wound (Ø = 2 cm) was created on each side of the neck in eight healthy horses. One randomly chosen wound received light treatment and the other served as an untreated control. Treatment duration was 4 minutes and 40 seconds (red light 95 seconds, 2.3 mW/cm2; NIR light 185 seconds, 6.4 mW/cm2) and was performed once daily on day 0‐4, 7‐11, 14‐18 and 21‐25. The wounds were photographed and evaluated using digital photoplanimetry on day 0, 1, 2, 3, 4, 7, 14, 21, 28 and 35. The degree of swelling was assessed with diagnostic ultrasound on the same days except the last recording was performed on day 36 instead of 35. Days to total healing was recorded. ANOVA was used for statistical analysis (P < .05).

Results

The wound area (P = .2‐.9) and degree of swelling (P = .2‐1.0) did not differ between treated and control groups on any day. There was a significant difference (P = .03) in healing time between control (49.0, 95% CI = 35.4‐62.6 days) and treated wounds (51.8, 95% CI = 38.7‐64.8 days).

Main limitations

The wounds were treated until day 25 and this study does not investigate the effect of a longer treatment period than 25 days.

Conclusions

The results of this study do not indicate any clinically relevant positive effect of pulsating visible red light and NIR light on the healing of experimental skin wounds in horses, compared with no treatment.
Using Generative Adversarial Networks as a Fast Forward Operator for Hydrogeological Inverse Problems
Authors: Dagasan Yasin , Juda Przemysław , Renard Philippe
Published: April 2020

Subsurface characterization using inverse techniques constitutes one of the fundamental elements of hydrogeological modeling applications. Available methods to solve inverse problems rely on a forward operator that predicts state variables for a given set of subsurface parameters. As the number of model parameters to be estimated increases, forward operations incur a significant computational demand. In this paper, we investigate the use of conditional generative adversarial networks (cGAN) as an emulator for the forward operator in the context of a hydrogeological inverse problem. We particularly investigate if the cGAN can be used to replace the forward operator used in the adaptive importance sampling method posterior population expansion (PoPEx) with reasonable accuracy and feasible computation requirement. The cGAN model trained on channelized geological structures has shown that the cGAN is able to reproduce the state variables corresponding to a certain parameter field. Hence, its integration in PoPEx yielded satisfactory results. In terms of the computational demand, the use of cGAN as a surrogate forward model reduces the required computational time up to 80% for the problem defined in the study. However, the training time required to create a model seems to be the major drawback of the method.
One social network, two perspectives: Social networks of people with Down syndrome based on self‐reports and proxy reports
Authors: Roll Anne E. , Koehly Laura M.
Published: April 2020

Background

For people with intellectual disabilities (ID), social networks play a key role in facilitating social inclusion, health, and quality of life. This study shows that a multi‐informant approach to collecting social network data improves our understanding of the social worlds of people with Down Syndrome (DS).

Method

A mixed methods egocentric network approach was employed to investigate 27 dyads comprised of people with DS and their family members as proxy reporters to examine variability in network characteristics across self‐ and proxy reports.

Results

The self‐reported total network size of people with DS was significantly smaller than the network size based on proxy reports. Significant differences were found between self‐ and proxy‐reported networks with respect to most relationship groups. Proxy informants reported more “paid staff”.

Conclusion

Our study showed that multiple perspectives on the social networks of people with DS are advantageous for researchers, policy makers, and practitioners.
Reduced Sirtuin1 signalling exacerbates diabetic mice hindlimb ischaemia injury and inhibits the protective effect of a liver X receptor agonist
Authors: Fan Wensi , Zhang Ran , Han Dong , Jiang Zhenhua , Li Shuang , Zhang Jibin , Li Yanhua , Wang Yabin , Cao Feng
Published: April 2020

Diabetes mellitus causes endothelial dysfunction, which further exacerbates peripheral arterial disease (PAD). Improving endothelial function via reducing endothelial oxidative stress (OS) may be a promising therapy for diabetic PAD. Activation of liver X receptor (LXR) inhibits excessive OS and provides protective effects on endothelial cells in diabetic individuals. Therefore, we investigated the effects of LXR agonist treatment on diabetic PAD with a focus on modulating endothelial OS. We used a streptozotocin‐induced diabetes mouse model combined with a hindlimb ischaemia (HLI) injury to mimic diabetic PAD, which was followed by LXR agonist treatment. In our study, the LXR agonist T0901317 protected against HLI injury in diabetic mice by attenuating endothelial OS and stimulating angiogenesis. However, a deficiency in endothelial Sirtuin1 (SIRT1) largely inhibited the therapeutic effects of T0901317. Furthermore, we found that the underlying therapeutic mechanisms of T0901317 were related to SIRT1 and non‐SIRT1 signalling, and the isoform LXRβ was involved in LXR agonist‐elicited SIRT1 regulation. In conclusion, LXR agonist treatment protected against HLI injury in diabetic mice via mitigating endothelial OS and stimulating cellular viability and angiogenesis by LXRβ, which elicited both SIRT1‐mediated and non‐SIRT1‐mediated signalling pathways. Therefore, LXR agonist treatment may be a promising therapeutic strategy for diabetic PAD.
Coupling of P–T–t–D histories of eclogite and metagreywacke—Insights to late Ordovician–Silurian crustal folding events recorded in the Beishan Orogen (NW China)
Authors: Soldner Jérémie , Štípská Pavla , Schulmann Karel , Yuan Chao , Anczkiewicz Robert , Sala Dariusz , Jiang Yingde , Zhang Yunying , Wang Xinyu
Published: April 2020

The Beishan complex is composed of orthogneiss and metagreywacke that both enclose bodies of eclogite and serves as a unique example for comparative petrological study of all these lithologies. The rocks show the earliest regional steep N‐S striking fabric (S2) preserved in low strain domains that are reworked by ubiquitous steep N‐NE dipping cleavage (S3). The eclogite shows an almost isotropic fabric defined by an M1 assemblage of Grt–Cpx–Amp–Qz–Rt–Ilm that is locally retrogressed to M2‐3 amphibolite facies mineral assemblages, with P–T peak at 20–21 kbar and 750–775°C and retrogression to 2–3kbar and 530–550°C. The typical mineral assemblage of the host metagreywackes is Bt–Ms–Pl–Qz−Chl–Ilm±Grt. Rare Al‐rich metagreywacke layers are composed of Grt–Ky–St±Sil−And–Bt–Ms–Pl–Qz±Chl±Rt–Ilm giving a P–T path with peak at 8–8.5kbar and ~670°C correlated with the S2 fabric and retrogression to ~2.5kbar and 525–550°C correlated with the S3 foliation. In two eclogite samples, the garnet‐whole rock‐clinopyroxene Lu–Hf isochrons give ages of 461.9±1.6 Ma and 462.0±6.2 Ma interpreted as reflecting average age of garnet formation, and Sm–Nd isochrons give ages of 453.6±2.7 Ma and 452.8±3.0 Ma interpreted as dating near‐peak metamorphism. In metagreywacke, in‐situ U–Pb dating of monazite gives two groups of ages of 445–440 Ma (Mnz cores) and 436–429 Ma (Mnz rims), interpreted as reflecting the metamorphic peak and retrogression. Our results show that eclogite was formed during Ordovician by subduction of a continental crust (D1). Eclogite and metagreywacke underwent partly decoupled P–T–t–D paths until their juxtaposition at mid‐crustal levels during a first late Ordovician–early Silurian D2 shortening. Coupling of their P–T–t–D paths occurred during exhumation in the Silurian and a second and orthogonal D3 shortening event. The data from the Beishan Orogen are consistent with a collisional intra‐Gondwanan orogen located south of the Central Asian Orogenic Belt.
Predicting Postpartum Hemorrhage After Vaginal Birth by Labor Phenotype
Authors: Erickson Elise N. , Lee Christopher S. , Carlson Nicole S.
Published: April 2020

Introduction

Postpartum hemorrhage (PPH) is an important contributor to maternal morbidity and mortality. Predicting which laboring women are likely to have a PPH is an active area of research and a component of quality improvement bundles. The purpose of this study was to identify phenotypes of labor processes (ie, labors that have similar features, such as duration and type of interventions) in a cohort of women who had vaginal births, estimate the likelihood of PPH by phenotype, and analyze how maternal and fetal characteristics relate to PPH risk by phenotype.

Methods

This study utilized the Consortium for Safe Labor dataset (2002‐2008) and examined term, singleton, vaginal births. Using 16 variables describing the labor and birth processes, a latent class analysis was performed to describe distinct labor process phenotypes.

Results

Of 24,729 births, 1167 (4.72%) women experienced PPH. Five phenotypes best fit the data, reflecting labor interventions, duration, and complications. Women who had shorter duration of admission after spontaneous labor onset (admitted in latent or active labor) had the lowest rate of PPH (3.8%‐3.9%). The 2 phenotypes of labor progress characterized by women who had complicated prolonged labors (spontaneous or induced) had the highest rate of PPH (8.0% and 12.0%, respectively). However, the majority of PPH (n = 881, 75%) occurred in the phenotypes with fewer complications. Prepregnancy body mass index did not predict PPH. Overall, the odds of PPH were highest among nulliparous women (odds ratio [OR], 1.52; 95% CI, 1.30‐1.77), as well as Black women (OR, 1.39; 95% CI, 1.13‐1.73) and Hispanic women (OR, 1.85; 95% CI, 1.56‐2.20). Within phenotypes, maternal race and ethnicity, nulliparity, macrosomia, hypertension, and depression were associated with increased odds of PPH.

Discussion

Women who were classified into a lower‐risk labor phenotype and still experienced PPH were more likely to be nulliparous, a person of color, or diagnosed with hypertension.
The bronchial tree of the human embryo: an analysis of variations in the bronchial segments
Authors: Fujii Sena , Muranaka Taiga , Matsubayashi Jun , Yamada Shigehito , Yoneyama Akio , Takakuwa Tetsuya
Published: April 2020

A classical study has revealed the general growth of the bronchial tree and its variations up to Carnegie stage (CS) 19. In the present study, we extended the morphological analysis CS by CS until the end of the embryonic period (CS23). A total of 48 samples between CS15 and CS23 belonging to the Kyoto Collection were used to acquire imaging data by performing phase‐contrast X‐ray computed tomography. Three‐dimensionally reconstructed bronchial trees revealed the timeline of morphogenesis during the embryonic period. Structures of the trachea and lobar bronchus showed no individual difference during the analyzed stages. The right superior lobar bronchus was formed after the generation of both the right middle lobar bronchus and the left superior lobar bronchus. The speed of formation of the segmental bronchi, sub‐segmental bronchi, and further generation seemed to vary among individual samples. The distribution of the end‐branch generation among five lobes was significantly different. The median branching generation value in the right middle lobe was significantly low compared with that of the other four lobes, whereas that of the right inferior lobe was significantly larger than that of both the right and left superior lobes. Variations found between CS20 and CS23 were all described in the human adult lung, indicating that variation in the bronchial tree may well arise during the embryonic period and continue throughout life. The data provided may contribute to a better understanding of bronchial tree formation during the human embryonic period.
Temporal mapping of the closure of the anterior fontanelle and contiguous sutures using computed tomography, in silico models of modern infants
Authors: Lottering Nicolene , Alston Clair L. , Barry Mark D. , MacGregor Donna M. , Gregory Laura S.
Published: April 2020

The aim of this study is to quantify and statistically model the age‐related decline in the fibrous connective tissue interface of the anterior fontanelle in modern Australian infants, using three‐dimensional, semi‐automated computed‐assisted design protocols. Non‐linear regression with variance models, using power functions, combined with quantile regression of the 5th and 95th population percentiles, were utilised to assess absolute anterior fontanelle surface area (AFSA) as a function of age, using multi‐slice cranial computed tomography scans obtained from 256 infants aged < 30 months (males: n = 126, females: n = 109) from Brisbane children’s hospitals. Normalised AFSA (NFSA), standardised for variation in cephalic size, followed a progressive decline from birth, the greatest velocity change occurring between the 3–6 and 6–9 month cohorts. Growth of the neurocranium is the most significant within the first 8 months postpartum, with a mean increase of 19.03 mm in maximum cranial length and 10.04 mm in breadth. Directionality of fontanelle closure, quantified using spline curves refutes fundamental assumptions that the anterior fontanelle is consistent with a quadrilateral, and contiguous sutures exhibit constant velocity of closure. The present study provides normative values for fontanelle size and diameters as well as new predictive non‐linear models for age substantiation, screening of developmental abnormalities and indicators of suspected child maltreatment in modern infants aged birth to 30 months.
Uncovering the impact of triadic relationships within a team on job performance: an application of balance theory in predicting feedback‐seeking behaviour
Authors: Lan Junbang , Huo Yuanyuan , Cai Zhenyao , Wong Chi‐Sum , Chen Ziguang , Lam Wing
Published: April 2020

Although a great deal of knowledge has accumulated about dyadic relationships (i.e., leader–member exchange (LMX) or team–member exchange (TMX)) within a team, employee behaviours that involve triadic relationships among focal employees, leaders, and teammates have seldom been investigated. Using balance theory, which describes triadic relationships from a power dependence perspective, in the current study, we explore how the interplay of LMX, TMX, and peers’ LMX jointly impacts employees’ feedback‐seeking behaviour (FSB) and subsequent job performance. By conducting a multilevel moderated polynomial regression on three‐wave, multi‐source data from 147 team members and their leaders (from 45 work teams), we found that the incongruence between LMX and TMX facilitates FSB when peers’ LMX or task interdependence is high. We also found an asymmetrical incongruence effect concerning the way in which individuals are more likely to seek feedback when LMX is worse than TMX, compared with when LMX is better than TMX. This differential effect is stronger when peers’ LMX or task interdependence is high. The interplay of LMX, TMX, peers’ LMX, and task interdependence eventually has an indirect effect on job performance through FSB. The results from a follow‐up study of 270 employees from 77 teams further confirm our predictions about the mechanism of balance theory. Specifically, the results indicate that when peers’ LMX is high, the incongruence between LMX and TMX decreases employees’ psychological safety.

Practitioner points

Our study highlights the importance of studying the triadic (LMX, TMX, and peers’ LMX) rather than dyadic relationships in a work team.

This study demonstrates that imbalanced relationship triads can influence employees in a positive way (i.e., motivate employees to conduct more change‐oriented proactive behaviours).

Our study’s findings show that feedback‐seeking behaviour is important in promoting job performance when it aims at changing the imbalanced social environment.

Our findings suggest practitioners should pay more attention to the role of task interdependence, which changes the power dependence structure of workplace relationships.
Hanging out in The Studio to challenge xenophobia: consolidating identities as community writers
Authors: Coban Osman , McAdam Julie E. , Arizpe Evelyn
Published: April 2020

This article examines findings from a Scottish Social Innovation Fund project carried out in an after‐school club known as The Studio. Researchers worked alongside artists to engage young people situated within their communities to challenge xenophobic discourses through the creation of positive narratives developed through story and arts‐based activities. The work used the “deep hang out theory” to generate a complex account of how the participants mediated the cultural tools surrounding them to produce a community text. Through engaging in an arts‐based process, the young writers and illustrators developed a sense of belonging within their communities, taking an active, engaged stance as literacy producers of texts that challenged xenophobic discourses. The lessons learned in this informal space are of relevance across contexts where young people wish to engage in creating positive narratives of community cohesion.
The Ralstonia solanacearum effector RipI induces a defence reaction by interacting with the bHLH93 transcription factor in Nicotiana benthamiana
Authors: Zhuo Tao , Wang Xue , Chen Zhengyu , Cui Haitao , Zeng Yanhong , Chen Yang , Fan Xiaojing , Hu Xun , Zou Huasong
Published: April 2020

Ralstonia solanacearum releases a set of effectors into plant cells that modify the host defence reaction. The role of the effector protein RipI during infection has not been elucidated. In this study, we demonstrated that transient overexpression of RipI induces the hypersensitive response (HR), up‐regulating the HR marker gene hin1, in Nicotiana benthamiana. Deletion of R. solanacearum ripI led to increased virulence in tomato (Solanum lycopersicum) plants. Through yeast two‐hybrid and pull‐down assays, we identified an interaction between the N. benthamiana transcription factor bHLH93 and RipI, both of which could be localized in the nucleus of Arabidopsis protoplasts. Silencing of bHLH93 markedly attenuated the RipI‐induced HR and induced expression of the PDF1.2 defence gene. These data demonstrate that the R. solanacearum effector RipI induces a host defence reaction by interacting with the bHLH93 transcription factor.
Serum growth differentiation factor 15 levels and clinical manifestations in patients with thiamine deficiency
Authors: Miyaue Noriyuki , Yabe Hayato , Nagai Masahiro
Published: April 2020

Background

Thiamine deficiency can cause a broad range of symptoms affecting the central nervous system. Although the precise mechanisms underlying these effects remain unclear, research suggests that mitochondrial dysfunction is involved. Some studies have reported that growth differentiation factor 15 (GDF15) is a useful biomarker for diagnosing mitochondrial disorder.

Aim

In the present study, we investigated the clinical associations between GDF15 and thiamine deficiency.

Methods

We measured serum GDF15 levels in four patients with thiamine deficiency, 28 healthy controls, five patients with mitochondrial disorder, three patients with neuromyelitis optica spectrum disorder, and one patient who presented with thiamine deficiency‐like symptoms despite normal blood levels of thiamine. GDF15 concentrations were measured via enzyme‐linked immunosorbent assay. Serum GDF15 levels were evaluated in consideration of clinical parameters including age, sex, and body mass index.

Results

Mean GDF15 levels were significantly higher in the thiamine deficiency (3990.5 pg/mL) and mitochondrial disorder groups (3363.2 pg/mL) than in the healthy control group (1062.0 pg/mL). Multiple regression analysis revealed that serum GDF15 levels were significantly associated with age and cognitive function in the healthy control group. The patient with thiamine deficiency‐like symptoms exhibited elevated serum GDF15 levels. In one patient with thiamine deficiency, GDF15 levels gradually decreased after initiating thiamine supplementation.

Conclusion

The present study demonstrates that serum GDF15 levels may be useful in the diagnosis and evaluation of patients with various manifestations of thiamine deficiency.
Altered rhizoctonia assemblages in grasslands on ex‐arable land support germination of mycorrhizal generalist, not specialist orchids
Authors: Vogt‐Schilb Hélène , Těšitelová Tamara , Kotilínek Milan , Sucháček Pavel , Kohout Petr , Jersáková Jana
Published: April 2020

Species‐rich seminatural grasslands in Central Europe have suffered a dramatic loss of biodiversity due to conversion to arable land, but vast areas are being restored. Population recovery of orchids, which depend on mycorrhizal fungi for germination, is however limited. We hypothesised that ploughing and fertilisation caused shifts in orchid mycorrhizal communities in soil and restricted orchid germination.

We examined edaphic conditions in 60 restored and seminatural grasslands, and germination success in 10 restored grasslands. Using a newly designed primer, we screened the composition of rhizoctonias in soil, seedlings and roots of seven orchid species.

Seminatural and restored grasslands differed significantly in nutrient amounts and rhizoctonia assemblages in soil. While Serendipitaceae prevailed in seminatural grasslands with a higher organic matter content, Ceratobasidiaceae were more frequent in phosphorus‐rich restored grasslands with increased abundance on younger restored sites. Tulasnellaceae displayed no preference. Germination success in restored grasslands differed significantly between orchid species; two mycorrhizal generalist species germinated with a broad range of rhizoctonias at most restored grasslands, while germination success of specialists was low.

Past agricultural practices have a long‐lasting effect on soil conditions and orchid mycorrhizal communities. Altered mycorrhizal availability may be the main reason for low germination success of specialist orchid species.
Comparative effectiveness of bariatric surgeries in patients with obesity and type 2 diabetes mellitus: A network meta‐analysis of randomized controlled trials
Authors: Ding Li , Fan Yuxin , Li Hui , Zhang Yalan , Qi Dongwang , Tang Shaofang , Cui Jingqiu , He Qing , Zhuo Chuanjun , Liu Ming
Published: April 2020

A network meta‐analysis of randomized controlled trials (RCTs) was performed to determine the hierarchies of different bariatric surgeries in patients with obesity and type 2 diabetes mellitus (T2DM), in terms of diabetes remission and cardiometabolic outcomes. Seventeen RCTs and six bariatric surgeries, including single anastomosis (mini) gastric bypass (mini‐GBP), biliopancreatic diversion without duodenal switch (BPD), laparoscopic‐adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux‐en‐Y gastric bypass (RYGBP), greater curvature plication (GCP) and nonsurgical treatments (NST) were included. Mini‐GBP, BPD, LSG, RYGBP and LAGB (from best to worst), as compared with NST, were all significantly associated with the remission of T2DM. For the follow‐up period > 3 years, BPD, mini‐GBP, RYGBP and LSG (from best to worst) were significantly superior to NST in achieving the remission of T2DM. For secondary outcomes, the overall ranking for bariatric surgeries was RYGBP > BPD > LSG > LAGB after comprehensively weighting glucose, weight, systolic and diastolic pressure, total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C). Mini‐GBP has the greatest probability of achieving diabetes remission in adults with obesity and T2DM, yet BPD was the most effective in long‐term diabetes remission. RYGBP appears to be the most favourable alternative treatment to manage patients with cardiometabolic conditions.
Saliva proteomics from children with caries at different severity stages
Authors: Guedes Sarah F.F. , Neves Beatriz G. , Bezerra Daniela S. , Souza Gustavo H.M.F. , Lima‐Neto Abelardo B.M. , Guedes Maria Izabel F. , Duarte Simone , Rodrigues Lidiany K. A.
Published: April 2020

Objective

To perform a comparative analysis of saliva protein profile of patients with early childhood caries at different levels of severity and caries‐free individuals.

Materials and methods

Stimulated saliva samples were collected from 126 children (2–6 years old), classified according to the ICDAS II, and divided into 3 groups (n = 42): caries‐free (CF), enamel caries (EC), and dentine caries (DC). Samples were digested and analyzed by nanoUPLC coupled with a mass spectrometry. Data analyses were conducted with Progenesis QI for Proteomics Software v2.0. Gene Ontology (GO) terms and protein–protein interaction analysis were obtained.

Results

A total of 306 proteins (≈6 peptides) were identified. Among them, 122 were differentially expressed in comparisons among children with different caries status. Out of the 122 proteins, the proteins E2AK4 and SH3L2 were exclusively present in groups CF and EC, respectively, and 8 proteins (HAUS4, CAH1, IL36A, IL36G, AIMP1, KLHL8, KLH13, and SAA1) were considered caries‐related proteins when compared to caries‐free children; they were up‐regulated proteins in the caries groups (EC and DC).

Conclusion

The identification of exclusive proteins for caries‐free or carious‐related conditions may help in understanding the mechanisms of caries and predicting risk as well as advancing in caries control or anti‐caries approaches.
Acetaminophen‐induced generalized fixed drug eruption in a 5‐year‐old girl
Authors: Genovese Giovanni , Gelmetti Carlo , Spigariolo Cristina , Colonna Cristiana
Published: April 2020

Acetaminophen is one of the most widely prescribed analgesic drugs. Fixed drug eruption, especially the pigmenting type, is reported in literature as a possible adverse event to acetaminophen in child. We hereby present a case of generalized fixed drug eruption due to acetaminophen intake in a 5‐year‐old dark‐skinned child.
Action research for innovation management: three benefits, three challenges, and three spaces
Authors: Ollila Susanne , Yström Anna
Published: April 2020

Given that the innovation landscape is changing, and new forms of organization and management are emerging, this study discusses the potential benefits of action research for innovation management (IM) as it provides closeness to living emergent systems, generates rich insights as well as knowledge for both rigorous theory development and change in practice. Drawing from a large‐scale action research study involving a complex collaborative organizational construct, we outline three challenges from employing action research: the process is both reflexive and progressive, the researcher is both an outsider and an insider, and the outcome is both general and specific. A model of three social spaces (the action research space, the academic space, and the practitioner space) is proposed to address the challenges and assist in navigating the multitude of processes, roles, and outcomes associated with action research. The study argues that action research for IM is well suited to exploring tacit aspects of practices and processes in the emergent or shifting study contexts to transform practices through interventions. Thus, if implemented carefully by experienced researchers, it can provide valuable data that are indispensable for theory development in the field of IM.
Prospects for a Monetary Union in the East Africa Community: Some Empirical Evidence
Authors: Caporale Guglielmo Maria , Gil‐Alana Luis
Published: April 2020

This paper examines generalised purchasing power parity (G‐PPP) and business cycle synchronisation in the East Africa Community with the aim of assessing the prospects for a monetary union. The univariate fractional integration analysis shows that the individual series exhibit unit roots and are highly persistent. The fractional bivariate cointegration tests suggest that there exist bivariate fractional cointegrating relationships between the exchange rate of the Tanzanian shilling and those of the other EAC countries, and also between the exchange rates of the Rwandan franc, the Burundian franc and the Ugandan shilling. The Fractionally Cointegrated Vector AutoRegressive (FCVAR) results imply the existence of a single cointegrating relationship between the exchange rates of the EAC countries. On the whole, there is evidence in favour of G‐PPP. In addition, there appears to be a high degree of business cycle synchronisation between these economies. On both grounds, one can argue that a monetary union should be feasible.
Intervention to reduce perceived loneliness in community‐dwelling older people
Authors: Rodríguez‐Romero Rocío , Herranz‐Rodríguez Carmen , Kostov Belchin , Gené‐Badia Joan , Sisó‐Almirall Antoni
Published: April 2020

Aim

We evaluated the reduction in perceived loneliness and depression and the increase in social support and quality of life in community‐dwelling lonely people aged >65 years included in a community intervention compared with nonlonely controls from the same urban area.

Design

Randomised clinical trial without blind evaluation.

Location

Urban area of Barcelona.

Participants

Community dwellers aged >65 years with loneliness identified by the primary care team.

Interventions

The primary care team together with community agents (municipal social services, community civil and religious associations) carried out 18 sessions developing activities including educational workshops, mindfulness, yoga, walking and visits to urban gardens.

Results

We included 55 patients (87% female, mean age 80.6 ± 6.86 years) of whom 82% had moderate and 18% severe loneliness. Six months postintervention, 48.3% of the intervention group did not feel lonely compared with 26.9% of controls (p = 0.001). Social support (DUKE‐UNC‐11) increased from 33.5 ± 9.3 to 41.4 ± 6.6, and mental health (SF‐12) from 36 ± 610.4 to 48 ± 11.1 and depressive symptoms (Yesavage test) decreased from 9.2 ± 3.6 to 5.2 ± 5.0 in the intervention but not the control group.

Conclusions

The intervention mainly reached people with moderate loneliness and significantly improved the perception of loneliness, depressive symptoms, social support and the mental health component of the quality of life. The intervention may be more suitable for people with moderate loneliness, but these types of activities may be difficult to accept by people with severe loneliness not related to the barriers to socialisation generated by ageing.
Effect of transdermal estradiol therapy on bone mineral density of amenorrheic female athletes
Authors: Nose‐Ogura Sayaka , Yoshino Osamu , Kanatani Mayuko , Dohi Michiko , Tabei Katsuyuki , Harada Miyuki , Hiraike Osamu , Kawahara Takashi , Osuga Yutaka , Fujii Tomoyuki
Published: April 2020

Background

The effects of transdermal estradiol treatment (HT) in amenorrheic athletes (AA) with low body weight (BW) and low bone mineral density (BMD) are unknown.

Purpose

To investigate whether HT increases BMD in AA with low BW and to compare the results with levels in AA who have recovered spontaneous menstruation (SM).

Methods

Female athletes (n = 151) were recruited at the Japan Institute of Sports Sciences and the University of Tokyo. All participants were divided into four groups: an AA group (untreated group) (n = 36), a HT group (n = 55), a SM group (n = 21), and an eumenorrheic athletes (EA) group (n = 39). Height, body weight, blood tests, and dual‐energy X‐ray absorptiometry were measured at baseline and after 12 months. The HT group was treated daily for 12 months with transdermal estrogen therapy. In addition, participants received oral progestin for 7 days once every 3 months.

Results

After 12 months, BMD in the AA group was significantly lower than at baseline; however, BMD in the other three groups was significantly higher than at baseline. The ratio of the change in BMD values before and after 12 months was −1.6 ± 3.2% for the AA group, 5.3 ± 8.7% for the HT group, 11.1 ± 8.9% for the SM group, and 2.3 ± 5.7% for the EA group. The rate of change in BMD values in the SM group was greater than that in the HT group.

Conclusion

HT increased BMD in AA with low BW, and the increase in those with SM was greater than that in those treated with HT.
Gender and Race in American Elections: From the Pathos of Prediction to the Power of Possibility1
Authors: Hughey Matthew W.
Published: April 2020

I provide first an overview of the predictions of the 2016 U.S. presidential election and the public penance paid by political oracles in the wake of the results. Next, I reflect on the social science emphasis on forecasting “who” will win and by “how much.” Third, I argue that our collective emphasis on prediction and realpolitik may obscure, if not stop, our ability to both understand how and why outcomes occur (by illuminating causal mechanisms at play) as well as how to imagine and form social worlds different than our current social relations (by alleviating or eliminating destructive leadership, policies, and rhetoric). Fourth, I call attention to some important gender and racial dynamics—all with the aim of better understanding how modern politics work in order to identify and pursue equitable movements, policies, and laws, rather than to simply (and problematically) make pre‐election seasons into carnivalesque fortune‐telling distractions. I conclude with recommendations on social science at the nexus of gender, race, and politics.
Entre la “guerra justa” y “una inútil masacre”: Benedicto XV, el papa desconocido
Authors: Echeverri Alberto
Published: April 2020

¿Son posibles en un mismo cristiano dosposiciones ético-teológicas distintas ante la mayor o menor licitud de la guerra? En el centenario del final de la I Guerra Mundial, hacer memoria de un personaje clave para la Iglesia Católica romana del momento pone de presente la disyuntiva a la que se vio enfrentado el genovés Giacomo Della Chiesa, primero como arzobispo de la Bolonia italiana, por la campaña de Libia (1911-1912), y luego como papa Benedicto XV, por la Gran Guerra (1914-1919). La investigación procede con una hermenéutica de documentos suyos y de contemporáneos, en Bolonia y el Vaticano; acude también a historiadores de su actuación en ambas investiduras. La conclusión revela el alcance que el asunto tuvo en el ejercicio pastoral de un creyente casi desconocido, y sugiere algunas líneas de examen del problema que la guerra continúa planteando a la teología cuando es adjetivada como justa.
Computational Model and Design of the Soft Tunable Lens Actuated by Dielectric Elastomer
Authors: Li Jinrong , Lv Xiongfei , Liu Liwu , Liu Yanju , Leng Jinsong
Published: April 2020

Inspired by the accommodation mechanism of the human eye, several soft tunable lenses have been fabricated and demonstrated the capability of controllable focus tuning. This paper presents a computational model of a dielectric elastomer-based soft tunable lens with a compact structure that is composed of a lens frame, two soft films, and the optically transparent fluid enclosed inside. The two soft films, respectively, serve as the active film and passive film. The active film is a dielectric elastomer film and can be coated with the annular electrode or circular electrode. The deformation of the lenses with both electrode configurations can all be formulated by a boundary value problem with different boundary conditions and be solved as the initial value problem using the shooting method. Two common failure modes of loss of tension and electrical breakdown are considered in the calculation of the lens. The computational results can well fit the experimental data. The focus tuning performances as well as the distributions of stretches, stresses, and electric field in the active films of the lenses with two different electrode configurations are compared. The influences of several parameters on the performances of the lenses are discussed, such that the tunable lens can be designed to have maximum focal length change or to be optimized based on different application requirements.