bluuebunny/crossref_metadata_2025_split 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

AimsSingle‐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.MethodsData 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.ResultsThe 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.ConclusionThis 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

AbstractObjectivesDentist‐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).MethodsA 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.ResultsResponse 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).ConclusionsThis 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

AbstractObjectiveTo 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).DesignProspective, interventional, randomized study.MethodsRandomized 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.ResultsIn 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).ConclusionCAT 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

AbstractPrimary 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

AbstractThe 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

AbstractIntroductionStandard 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.ObjectivesWe 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.MethodsThirty 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 conclusionThe “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

AbstractBackgroundLight‐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.ObjectivesTo investigate if treatment with pulsating visible red light (λ ≈ 637 nm) and near‐infrared (NIR) light (λ ≈ 956 nm) affects wound healing.Study designRandomised blinded controlled experimental study.MethodsA 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).ResultsThe 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 limitationsThe wounds were treated until day 25 and this study does not investigate the effect of a longer treatment period than 25 days.ConclusionsThe 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

AbstractSubsurface 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

AbstractBackgroundFor 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).MethodA 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.ResultsThe 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”.ConclusionOur 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

AbstractDiabetes 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

AbstractThe 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

IntroductionPostpartum 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.MethodsThis 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.ResultsOf 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.DiscussionWomen 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

AbstractA 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.