bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIDD0301 – A first‐in‐class anti‐inflammatory asthma drug targets GABAA receptors without causing systemic immune suppression
Authors: Zahn Nicolas M. , Huber Alec T. , Mikulsky Brandon N. , Stepanski Mae E. , Kehoe Alexander S. , Li Guanguan , Schussman Melissa , Rashid Roni Mohammed S. , Kodali Revathi , Cook James M. , Stafford Douglas C. , Steeber Douglas A. , Arnold Leggy A. 
Published: January 2019

AbstractWe report a 28‐day repeat dose immunotoxicity evaluation of investigational drug MIDD0301, a novel oral asthma drug candidate that targets gamma amino butyric acid type A receptors (GABAAR) in the lung. The study design employed oral administration of mice twice daily throughout the study period with 100 mg/kg MIDD0301 mixed in peanut butter. Compound dosing did not reveal signs of general toxicity as determined by animal weight, organ weight or haematology. Peanut butter plus test drug (in addition to ad libitum standard rodent chow) did not affect weight gain in the adult mice, in contrast to weight loss in 5 mg/kg prednisone‐treated mice. Spleen and thymus weights were unchanged in MIDD0301‐treated mice, but prednisone significantly reduced the weight of those organs over the 28‐day dosing. Similarly, no differences in spleen or thymus histology were observed following MIDD0301 treatment, but prednisone treatment induced morphological changes in the spleen. The number of small intestine Peyer's patches was not affected by MIDD0301 treatment, an important factor for orally administered drugs. Circulating lymphocyte, monocyte and granulocyte numbers were unchanged in the MIDD0301‐treated animals, whereas differential lymphocyte numbers were reduced in prednisone‐treated animals. MIDD0301 treatment did not alter IgG antibody responses to dinitrophenyl following dinitrophenyl‐keyhole limpet haemocyanin immunization, indicating that systemic humoral immune function was not affected. Taken together, these studies show that repeated daily administration of MIDD0301 is safe and not associated with adverse immunotoxicological effects in mice.
A Bayesian Hierarchical Model Estimating CACE in Meta-Analysis of Randomized Clinical Trials With Noncompliance
Authors: Zhou Jincheng , Hodges James S. , Suri M. Fareed K. , Chu Haitao 
Published: January 2019

AbstractNoncompliance to assigned treatment is a common challenge in analysis and interpretation of randomized clinical trials. The complier average causal effect (CACE) approach provides a useful tool for addressing noncompliance, where CACE is defined as the average difference in potential outcomes for the response in the subpopulation of subjects who comply with their assigned treatments. In this article, we present a Bayesian hierarchical model to estimate the CACE in a meta-analysis of randomized clinical trials where compliance may be heterogeneous between studies. Between-study heterogeneity is taken into account with study-specific random effects. The results are illustrated by a re-analysis of a meta-analysis comparing the effect of epidural analgesia in labor versus no or other analgesia in labor on the outcome cesarean section, where noncompliance varied between studies. Finally, we present simulations evaluating the performance of the proposed approach and illustrate the importance of including appropriate random effects and the impact of over- and under-fitting.
Fast Likelihood-Based Inference for Latent Count Models Using the Saddlepoint Approximation
Authors: Zhang W. , Bravington M. V. , Fewster R. M. 
Published: January 2019

AbstractLatent count models constitute an important modeling class in which a latent vector of counts, , is summarized or corrupted for reporting, yielding observed data where is a known but non-invertible matrix. The observed vector generally follows an unknown multivariate distribution with a complicated dependence structure. Latent count models arise in diverse fields, such as estimation of population size from capture-recapture studies; inference on multi-way contingency tables summarized by marginal totals; or analysis of route flows in networks based on traffic counts at a subset of nodes. Currently, inference under these models relies primarily on stochastic algorithms for sampling the latent vector , typically in a Bayesian data-augmentation framework. These schemes involve long computation times and can be difficult to implement. Here, we present a novel maximum-likelihood approach using likelihoods constructed by the saddlepoint approximation. We show how the saddlepoint likelihood may be maximized efficiently, yielding fast inference even for large problems. For the case where has a multinomial distribution, we validate the approximation by applying it to a specific model for which an exact likelihood is available. We implement the method for several models of interest, and evaluate its performance empirically and by comparison with other estimation approaches. The saddlepoint method consistently gives fast and accurate inference, even when is dominated by small counts.
Cancer core length from targeted biopsy: an index of prostate cancer volume and pathological stage
Authors: Simopoulos Demetrios N. , Sisk Anthony E. , Priester Alan , Felker Ely R. , Kwan Lorna , Delfin Merdie K. , Reiter Robert E. , Marks Leonard S. 
Published: January 2019

ObjectiveTo study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)‐visible index lesions, to volume of that tumour found at radical prostatectomy (RP).Patients and MethodsIn all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an indexMRI‐visible lesion (TB) and 69 in whom MCCL came from a non‐targeted lesion (non‐targeted biopsy [NTB]).MRIwas 3‐T multi‐parametric and biopsy was viaMRI‐ultrasonographyfusion.ResultsIn the TB group, MCCL correlated with volume of clinically significant index tumours (ρ = 0.44–0.60,P < 0.01). The correlation was similar for first and repeat biopsy and for transition and peripheral zone lesions (ρ = 0.42–0.49,P < 0.01). No correlations were found in the NTB group. TB MCCL (6–10 and >10 mm) andMRIlesion diameter (>20 mm) were independently associated with tumour volume. TB MCCLs >10 mm and Gleason scores >7 were each associated with pathological T3 disease (odds ratios 5.73 and 5.04, respectively), butMRIlesion diameter lesion was not.ConclusionsMCCL on a TB from anMRI‐visible lesion is an independent predictor of both cancer volume and pathological stage. This relationship does not exist for MCCL from a NTB core. Quantifying CCL onMRI‐TBs may have a value, not previously described, to risk‐stratify patients with prostate cancer before treatment.
Sanctuary Inter/rupted : Borders, illegalization, and unbelonging
Authors: Fakhrashrafi Mitra , Kirk Jessica P. , Gilbert Emily 
Published: January 2019

Key Messages

Sanctuary Inter/rupted, a group exhibit by Way Past Kennedy Road, explored issues of internal borders, illegalization, and unbelonging in Toronto.
We focus on how artists in the Sanctuary Inter/rupted exhibit unsettled whitewashing logics of belonging and contested the limits of liberal sanctuary city movements.
We expand the ways that racial justice is understood and practiced in sanctuary city movement organizing.
Bennett acceptance ratio method to calculate the binding free energy of BACE1 inhibitors: Theoretical model and design of new ligands of the enzyme
Authors: Gutiérrez Margarita , Vallejos Gabriel A. , Cortés Magdalena P. , Bustos Carlos 
Published: January 2019

AbstractIn recent years, the design, development, and evaluation of several inhibitors of the BACE1 enzyme, as part of Alzheimer's treatment, have gathered the scientific community's interest. Here, a linear regression model was built using binding free energy calculations through the Bennett acceptance ratio method for 20 known inhibitors of the BACE1 enzyme, with a Pearson coefficient of R = 0.88 and R2 = 0.78. The validation of this model was verified employing eight additional random inhibitors, which also gave a linear correlation with R = 0.97 and R2 = 0.93. Furthermore, this linear regression model was also used for proposing the structure of four potential BACE1 inhibitors, and the most active of them gave a theoretical Kd = 10 nM. However, these molecules have not been synthesized yet. Our team used a total time of more than 800 ns for the Molecular Dynamics to carry out this study, and all the software used were freely available.
Depression among Chinese Left‐Behind Children: A systematic review and meta‐analysis
Authors: Ding Lanyan , Yuen Lok‐Wa , Buhs Eric S. , Newman Ian M. 
Published: January 2019

AbstractBackgroundIn China, there are approximately 70 million children, nearly 25% of the child population, who are left behind in the care of other family members when their parents migrate to urban areas, for increased economic opportunities. This paper presents a systematic review and a meta‐analysis of studies that have examined the phenomenon of depression among these left‐behind children (LBC).MethodsSix hundred three papers published between 2000 and 2017 were retrieved from five databases (China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, and Web of Science).ResultsTwenty‐one studies (18 in Chinese and 3 in English) met the criteria for inclusion in this meta‐analysis. The pooled estimate of depression among LBC was 26.4%. A significant heterogeneity has been found in reported findings, and this heterogeneity was associated with three types of study characteristics, including using an unclear definition of LBC and using invalidated depression instruments, and the geographic location.ConclusionsThe risk of mental health problems among this large number of LBC suggests the need to quantify the extent and distribution of their mental health state. Implications for methodological improvements for future research have been discussed.
Supporting children and young people to assume responsibility from their parents for the self‐management of their long‐term condition: An integrative review
Authors: Nightingale Ruth , McHugh Gretl , Kirk Susan , Swallow Veronica 
Published: January 2019

AbstractBackgroundChildren and young people with long‐term conditions (LTCs) are usually dependent on, or share management with, their families and are expected to develop self‐management skills as they mature. However, during adolescence, young people can find it challenging to follow prescribed treatment regimens resulting in poor clinical outcomes. Though reviews have looked at children's and parents' experiences of self‐management, none have explicitly examined the parent‐to‐child transfer of self‐management responsibility.MethodsAn integrative review was conducted with the aim of exploring the parent‐to‐child transfer of LTC self‐management responsibility, through addressing two questions: (a) How do children assume responsibility from their parents for self‐management of their LTC? (b) What influences the parent‐to‐child transfer of this responsibility? Eight databases were searched for papers published from 1995 to 2017. Methodological quality was assessed; included papers were synthesized to identify themes.ResultsTwenty‐nine papers were identified. Most papers used qualitative designs and focused on children with diabetes. Participants were predominantly children and/or parents; only two studies included health professionals. Assuming self‐management responsibility was viewed as part of normal development but was rarely explored within the context of the child gaining independence in other areas of their life. Children and parents adopted strategies to help the transfer, but there was limited evidence around health professionals' roles and ambivalence around what was helpful. There was a lack of clarity over whether children and parents were aiming for shared management, or self‐management, and whether this was a realistic or desired goal for families. Multiple factors such as the child, family, social networks, health professional, and LTC influenced how a child assumed responsibility.ConclusionsEvidence suggests that the parent‐to‐child transfer of self‐management responsibility is a complex, individualized process. Further research across childhood LTCs is needed to explore children's, parents', and professionals' views on this process and what support families require as responsibilities change.
Measures for social support in raising a child with a disability: A scoping review
Authors: Mantri‐Langeveldt Anushka , Dada Shakila , Boshoff Kobie 
Published: January 2019

AbstractBackgroundThe benefits of social support for caregivers raising a child with a disability have been identified in the literature. These benefits include the improvement of the mental and physical well‐being of the caregivers, improvement in caregiving styles, and overall improvement of family quality of life. Whilst the benefits of social support are widely reported, the definitions and measures of social support in the literature are varied.MethodA scoping review was therefore undertaken to identify and describe the tools used to measure social support of primary caregivers (i.e., parents or grandparents) raising a child (0–18 years) with a congenital disability in international studies. Ten databases were systematically searched.ResultsSixteen studies were included in the review, from which nine social support measures were identified. Attributes of the measures were searched from their referenced papers and described in terms of their reported psychometric properties.ConclusionsThrough the identification of the measures of social support and ensuring its accurate measurement, direction can be provided for intervention by allowing professionals to detect and address social support available. Future recommendations for research are made.
Somatic symptoms in children who have a parent with cancer: A systematic review
Authors: Hauskov Graungaard Anette , Roested Bendixen Christina , Haavet Ole Rikard , Smith‐Sivertsen Tone , Mäkelä Marjukka 
Published: January 2019

AbstractBackgroundThis systematic review explored the occurrence and types of somatic symptoms in children (0–20 years) who have experienced parental cancer.MethodsWe complemented a systematic literature search from PubMed and PsycInfo with a reference search. We identified 1,694 articles, which were independently screened by two authors; they further evaluated potentially relevant papers for quality and extracted the data. We found nine relevant studies (10 publications) on altogether 672 children with a parent who had cancer; four studies included a control group.ResultsThe studies typically focused on children's psychosocial reactions on parental cancer rather than somatic complaints, so symptom prevalence cannot be reliably summarized. Several studies were small, and the types of somatic symptoms were only specified in five studies. Somatic symptoms were reported as a measure of emotional reactions in the remaining four studies. Three studies provided longitudinal data.The main types of specific symptoms reported were eating problems, pain, sleeping troubles, and bed‐wetting. Children of cancer patients tended to show an increase of unspecified somatic symptoms and pain, but evidence was inconsistent. There was a tendency that somatic complaints were associated with increased emotional distress in the children. The material did not allow for separate analysis by age group or bereavement status.ConclusionsChildren in families with parental cancer may present with somatic complaints, but the prevalence and significance is not possible to estimate due to very sparse research in this area. Health professionals or counselling providers should not overlook this possible sign of distress. Qualitative studies report significant health anxiety in these children; this may represent a specific topic for counselling in this population. Targeted studies are needed to evaluate the prevalence and significance of somatic symptoms, and especially vulnerable groups need to be identified.
Natural killer cell expression of Ki67 is associated with elevated serum IL-15, disease activity and nephritis in systemic lupus erythematosus
Authors: Hudspeth K , Wang S , Wang J , Rahman S , Smith M A , Casey K A ,   Autoimmunity Molecular Team, Manna Z , Sanjuan M , Kolbeck R , Hasni S , Ettinger R , Siegel R M 
Published: January 2019

Summary
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder whose pathology involves multiple immune cell types, including B and T lymphocytes as well as myeloid cells. While it is clear that autoantibody-producing B cells, as well as CD4+ T cell help, are key contributors to disease, little is known regarding the role of innate lymphoid cells such as natural killer (NK) cells in the pathogenesis of SLE. We have characterized the phenotype of NK cells by multi-color flow cytometry in a large cohort of SLE patients. While the overall percentage of NK cells was similar or slightly decreased compared to healthy controls, a subset of patients displayed a high frequency of NK cells expressing the proliferation marker, Ki67, which was not found in healthy donors. Although expression of Ki67 on NK cells correlated with Ki67 on other immune cell subsets, the frequency of Ki67 on NK cells was considerably higher. Increased frequencies of Ki67+ NK cells correlated strongly with clinical severity and active nephritis and was also related to low NK cell numbers, but not overall leukopenia. Proteomic and functional data indicate that the cytokine interleukin-15 promotes the induction of Ki67 on NK cells. These results suggest a role for NK cells in regulating the immune-mediated pathology of SLE as well as reveal a possible target for therapeutic intervention.
Effect of pembrolizumab on CD4+CD25+, CD4+LAP+ and CD4+TIM-3+ T cell subsets
Authors: Toor S M , Sasidharan Nair V , Pfister G , Elkord E 
Published: January 2019

Summary
Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4+CD25+ regulatory T cells (conventional Treg) with T cells expressing T cell immunoglobulin-3+ (TIM-3+) and latency-associated peptide (LAP)+ T cells. We found that LAP-expressing T cells were more suppressive than conventional Treg, but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of Treg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome Treg resistance to ICI.
A dynamic analysis of cost‐share agri‐environmental programs
Authors: Vercammen James 
Published: January 2019

AbstractThe purpose of this paper is to theoretically examine the efficiency of a cost‐share agri‐environmental program through a farm life cycle lens. Faced with a growing environmental impact from agricultural production, the farmer must decide when and how aggressively to invest in environmental capital. The steady state of the optimal control problem reveals the trade‐off between allocating farm profits to consumption versus environmental improvements. A payment from a cost‐share program reduces the time to investment in environmental capital, and also permanently increases the farmer's level of investment. A lack of targeting results in inframarginal farmers being paid more than the minimum amount that is required to induce investment. The portion of both the marginal payment and the average payment that induces new investment declines as the government's share of the payment increases, and this decline decreases overall program efficiency. Despite this inefficiency, a larger payment from a cost‐share program is shown to decrease the farm's environmental impact in both the short and long run.
Quantifying habitat losses and gains made by U.S. Species Conservation Banks to improve compensation policies and avoid perverse outcomes
Authors: Sonter Laura J. , Barnes Megan , Matthews Jeffrey W. , Maron Martine 
Published: January 2019

AbstractCompensation policies seek to counterbalance biodiversity losses caused by development; however, their effectiveness is rarely tested. We examined U.S. Species Conservation Banks (SCBs) in California, a compensation program initiated 30 years ago. We quantified the effect of 59 SCBs (15,350 ha) on habitat extent using statistical matching methods. SCBs averted a small, yet significant, amount of habitat loss (62 ha) between 2001 and 2011. However, unexpectedly, SCBs also averted significant habitat gains (1,424 ha). It is not possible to determine if losses averted by SCBs equaled losses caused by development for which credits were sold (because records of the latter do not exist), but estimated averted gains were 35 times greater than averted losses. To improve practice, SCBs must be designed to achieve outcomes that are additional and avoid crowding out other programs incentivizing statewide conservation goals.
Prevalence of diabetes among children treated with growth hormone in Israel
Authors: Lutski M. , Zucker I. , Zadik Z. , Libruder C. , Blumenfeld O. , Shohat T. , Laron Z. 
Published: January 2019

AbstractAimsTo determine the long‐term risk of diabetes in a cohort of children treated with recombinant human growth hormone in Israel, using data from the Israeli National Diabetes Register.MethodsBetween 1988 and 2009, 2513 children were approved for growth hormone treatment. They were assigned to one of two groups. The first group included children treated for isolated growth hormone deficiency and who were small for gestational age and the second included those treated for multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome or Prader–Willi syndrome. The cohort was cross‐linked with the Israeli National Diabetes Register for 2014 (mean follow‐up duration 12.1±5.3 years), and prevalent cases of diabetes were identified. Standardized prevalence ratios for diabetes were calculated for people aged 10–29 years.ResultsIn 2014, a total of 23 individuals were identified with diabetes (four with pre‐existing diabetes, seven developed diabetes before age 17 years and 12 developed it at a later age). In the isolated growth hormone deficiency and small‐for‐gestational‐age group there was no difference in the prevalence of diabetes compared with the general population (standardized prevalence ratio 2.05, 95% CI 0.94–3.89). In the group that included people with multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome and Prader–Willi syndrome there was a significantly higher diabetes prevalence (standardized prevalence ratio 11.94, 95% CI 6.53–20.00) compared with the general population.ConclusionsNo difference in diabetes prevalence was found in the isolated growth hormone deficiency and small‐for‐gestational‐age group, compared with the general population. Children treated with growth hormone with pre‐existing risk factors had an increased prevalence of diabetes. It is advisable to monitor blood glucose levels closely during and after growth hormone treatment, especially in such children.