bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB Signaling in Astrocytes Modulates Brain Inflammation and Neuronal Injury Following Sequential Exposure to Manganese and MPTP During Development and Aging
Authors: Hammond Sean L , Bantle Collin M , Popichak Katriana A , Wright Katie A , Thompson Delaney , Forero Catalina , Kirkley Kelly S , Damale Pranav U , Chong Edwin K P , Tjalkens Ronald B 
Published: July 2020

Abstract
Chronic exposure to manganese (Mn) is associated with neuroinflammation and extrapyramidal motor deficits resembling features of Parkinson’s disease. Activation of astrocytes and microglia is implicated in neuronal injury from Mn but it is not known whether early life exposure to Mn may predispose glia to more severe inflammatory responses during aging. We therefore examined astrocyte nuclear factor kappa B (NF-κB) signaling in mediating innate immune inflammatory responses during multiple neurotoxic exposures spanning juvenile development into adulthood. MnCl2 was given in drinking water for 30-day postweaning to both wildtype mice and astrocyte-specific knockout (KO) mice lacking I kappa B kinase 2, the central upstream activator of NF-κB. Following juvenile exposure to Mn, mice were subsequently administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 4 months of age. Animals were evaluated for behavioral alterations and brain tissue was analyzed for catecholamine neurotransmitters. Stereological analysis of neuronal and glial cell counts from multiple brain regions indicated that juvenile exposure to Mn amplified glial activation and neuronal loss from MPTP exposure in the caudate-putamen and globus pallidus, as well as increased the severity of neurobehavioral deficits in open field activity assays. These alterations were prevented in astrocyte-specific I kappa B kinase 2 KO mice. Juvenile exposure to Mn increased the number of neurotoxic A1 astrocytes expressing C3 as well as the number of activated microglia in adult mice following MPTP challenge, both of which were inhibited in KO mice. These results demonstrate that exposure to Mn during juvenile development heightens the innate immune inflammatory response in glia during a subsequent neurotoxic challenge through NF-κB signaling in astrocytes.
A Tiered Female Ovarian Toxicity Screening Identifies Toxic Effects of Checkpoint Kinase 1 Inhibitors on Murine Growing Follicles
Authors: Xu Jingshan , Wang Yingzheng , Kauffman Alexandra E , Zhang Yaqi , Li Yang , Zhu Jie , Maratea Kimberly , Fabre Kristin , Zhang Qiang , Woodruff Teresa K , Xiao Shuo 
Published: July 2020

AbstractOvarian toxicity (ovotoxicity) is one of the major side effects of pharmaceutical compounds for women at or before reproductive age. The current gold standard for screening of compounds’ ovotoxicity largely relies on preclinical investigations using whole animals. However, in vivo models are time-consuming, costly, and harmful to animals. Here, we developed a 3-tiered ovotoxicity screening approach starting from encapsulated in vitro follicle growth (eIVFG) and screened for the potential ovotoxicity of 8 preclinical compounds from AstraZeneca (AZ). Results from Tiers 1 to 2 screenings using eIVFG showed that the first 7 tested AZ compounds, AZ-A, -B, -C, -D, -E, -F, and -G, had no effect on examined mouse follicle and oocyte reproductive outcomes, including follicle survival and development, 17β-estradiol secretion, ovulation, and oocyte meiotic maturation. However, AZ-H, a preclinical compound targeting the checkpoint kinase 1 inhibitor to potentiate the anticancer effects of DNA-damaging agents, significantly promoted granulosa cell apoptosis and the entire growing follicle atresia at clinically relevant concentrations of 1 and 10 μM. The more targeted explorations in Tier 2 revealed that the ovotoxic effect of AZ-H primarily resulted from checkpoint kinase 1 inhibition in granulosa cells. Using in vivo mouse model, the Tier 3 screening confirmed the in vitro ovotoxicities of AZ-H discovered in Tiers 1 and 2. Also, although AZ-H at 0.1 μM alone was not ovotoxic, it significantly exacerbated gemcitabine-induced ovotoxicities on growing follicles. Taken together, our study demonstrates that the tiered ovotoxicity screening approach starting from eIVFG identifies and prioritizes pharmaceutical compounds of high ovotoxicity concern.
Point-of-Care Analysis of Neutrophil Phenotypes: A First Step Toward Immuno-Based Precision Medicine in the Trauma ICU
Authors: Spijkerman Roy , Hesselink Lillian , Bongers Suzanne , van Wessem Karlijn J.P. , Vrisekoop Nienke , Hietbrink Falco , Koenderman Leo , Leenen Luke P.H. 
Published: July 2020

Objectives:
The amount of tissue damage and the amplitude of the immune response after trauma are related to the development of infectious complications later on. Changes in the neutrophil compartment can be used as read out of the amplitude of the immune response after trauma. The study aim was to test whether 24/7 point-of-care analysis of neutrophil marker expression by automated flow cytometry can be achieved after trauma.

Design:
A prospective cohort study was performed. Polytrauma patients who developed infectious complications were compared with polytrauma patients who did not develop infectious complications.

Setting:
The study was performed in a level 1 trauma center.

Patients:
All trauma patients presented in the trauma bay were included.

Interventions:
An extra blood tube was drawn from all patients. Thereafter, a member of the trauma team placed the blood tube in the fully automated flow cytometer, which was located in the corner of the trauma room. Next, a modified and tailored protocol for this study was automatically performed.

Main Results:
The trauma team was able to successfully start the point-of-care automated flow cytometry analysis in 156 of 164 patients, resulting in a 95% success rate. Polytrauma patients who developed infectious complications had a significantly higher %CD16dim/CD62Lbright neutrophils compared with polytrauma patients who did not develop infectious complications (p = 0.002). Area under the curve value for %CD16dim/CD62Lbright neutrophils is 0.90 (0.83–0.97).

Conclusions:
This study showed the feasibility of the implementation of a fully automated point-of-care flow cytometry system for the characterization of the cellular innate immune response in trauma patients. This study supports the concept that the assessment of CD16dim/CD62Lbright neutrophils can be used for early detection of patients at risk for infectious complications. Furthermore, this can be used as first step toward immuno-based precision medicine of polytrauma patients at the ICU.
The Get-Up! study: adiposity and blood pressure in Australian toddlers
Authors: Sousa-Sá Eduarda , Zhang Zhiguang , Pereira João R. , Veldman Sanne L.C. , Okely Anthony D. , Santos Rute 
Published: July 2020

Abstract

Background:
Because the elevated blood pressure (BP) in childhood is strongly associated with overweight and is a risk factor for later cardiovascular disease, a need to comprehend the early development of BP and its association with overweight is needed. We assessed differences of BP by weight status in Australian toddlers.

Methods:
From the Get-Up! Study in Australia, this sample included 265 toddlers (136 boys), aged 19.6 ± 4.2 months. BP was measured with a digital vital signs monitor. Participants were categorized as nonoverweight and overweight according to the World Health Organization definition for body mass index (BMI). Physical activity was captured with activPAL accelerometers, during childcare hours. To test differences in BP between nonoverweight and overweight children, we performed an analysis of covariance adjusting for sex, age, physical activity, and socioeconomic status.

Results:
Children with overweight showed higher z systolic BP values (P = .042 for BMI and P = .023 for waist circumference) when compared to nonoverweight children. However, no differences were found for z diastolic BP levels, between overweight and nonoverweight children. After adjustments for potential confounders (socioeconomic status, physical activity, sex, and age), there were no significant differences in BP variables between BMI and waist circumference groups.

Conclusions:
No associations between adiposity and BP levels were found in this sample. The unadjusted results, however, showed that children with higher levels of adiposity (BMI and waist circumference) exhibited higher levels of BP. Additional research is needed to determine which environmental and genetic factors might contribute to pediatric hypertension, particularly among toddlers.
Diagnosis, treatment, and work impact of iron deficiency anemia in a Portuguese urban community
Authors: Norton Pedro , Araújo Natália , Pinho Paulo , Costa Gomes Joana , Silva Carla , Gama Céline , Barbosa Manuel , Ferreira Pedro , Cunha Sara , Moreira Sara , Martins Sílvia , Faria Sofia , Sousa Sophie , Figueiras Alves Nuno , Lunet Nuno 
Published: July 2020

Abstract

Introduction:
Little is known about iron deficiency anemia (IDA)'s treatment in Portugal. We aim to estimate the proportion of anemia, IDA, and iron deficiency without anemia; characterize the diagnostic procedures and prescription patterns; assess anemia's impact over work absenteeism, in a Local Health Unit.

Material and methods:
Cross-sectional study that evaluated complete blood counts, iron-containing prescriptions, comorbidities, economic failure, and disability certificates issued in 2015 at the Local Health Unit.

Results:
We evaluated 62,794 complete blood count. The proportion of anemia was 16.5%, higher in patients with economic failure, pregnant women, and patients with congestive heart failure. Of the patients with anemia 87.8% had not serum iron and/or ferritin dosing, and of those with serum iron/ferritin levels tested 50.6% had IDA. IDA was higher in pregnant women, women aged ≥15 years and in patients with congestive heart failure. Approximately 56.2% of patients with IDA did not receive iron-containing medication, and in 38% of the cases the prescribed dose was subtherapeutic. Of the total iron prescriptions 44.1% were association therapies. Anemia accounted for 5.2% of the disability certificates issued in 2015 (1749 workdays lost).

Discussion:
Most patients with anemia are not being adequately evaluated and a major proportion does not undergo treatment or has subtherapeutic doses of iron. These results may explain the anemia's impact on work capacity.

Conclusion:
This is one of the largest studies on anemia in Portugal. An effort to adapt to the established recommendations is urged, to minimize the consequences of this disease.
Reproductive trajectories and social-biological dimensions in parenthood: Portuguese version of the Meaning of Parenthood scale
Authors: Henriques Ana , Samorinha Catarina , Ramos Elisabete , Silva Susana 
Published: July 2020

Abstract

Background:
Public meanings attributed to parenthood may shape individuals’ family planning and how involuntary childlessness is supported by governmental policies. This study aimed to evaluate the influence of reproductive trajectories and gender in the meanings attributed to parenthood, and to assess the psychometric characteristics of the Portuguese version of the Meaning of Parenthood (MOP) scale.

Methods:
The sample comprised 754 participants: 246 young adults without children; 51 fathers and 159 mothers of adolescent children conceived spontaneously; and 149 infertile heterosexual couples. The scale was self-administered. Higher scores indicate attributing greater importance to parenthood to fulfill identity needs at individual, marital and social levels. Psychometric characteristics were analyzed through exploratory factor analysis; Cronbach alpha (α) assessed internal consistency.

Results:
Two dimensions of the MOP scale emerged, with good internal consistency (α ≥ 0.70): biological (importance of parenthood to fulfill reproductive needs as a biological being); social (importance of parenthood arising from social reproduction). Young adults attributed less importance to parenthood to fulfill both biological and social needs. The biological dimension was valued more than the social dimension in all subsamples; men highly valued the biological dimension compared to women.

Conclusions:
Family planning needs to focus on a reasonable balance between biological and social dimensions of parenthood. The reinforcement of public policies providing the necessary conditions for human reproduction is essential to reverse declining fertility rates.
Efficacy of fulvestrant 500 mg in Chinese postmenopausal women with advanced/recurrent breast cancer and factors associated with prolonged time-to-treatment failure
Authors: Huang Jian , Huang Ping , Shao Xi-ying , Sun Yan , Lei Lei , Lou Cai-jin , Ye Wei-wu , Chen Jun-qing , Cao Wen-ming , Huang Yuan , Zheng Ya-bing , Wang Xiao-jia , Chen Zhan-hong 
Published: July 2020

Abstract
This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure.
Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed.
Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively).
Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.
Association of RANTES gene polymorphisms with susceptibility to childhood asthma
Authors: Zhang Yan-Qin , Gao Xiu-Xiang 
Published: July 2020

AbstractBackground:Previous investigations have illustrated that regulated upon activation, normal T-cell expressed and secreted (RANTES) polymorphisms are linked to susceptibility to childhood asthma; nevertheless, the findings continue to be controversial. Accordingly, we conducted the present meta-analysis to clarify the impact of RANTES genetic polymorphisms (-403G/A and -28C/G) on childhood asthma vulnerability.Methods:A search for published literature was performed using the PubMed, EMBASE, Chinese National Infrastructure, Cochrane Library, Scopus, Web of Science, and WanFang databases and selected in the form of PICOS (participants, interventions, comparisons, outcomes, and study design) to identify all eligible research works. The link between RANTES genetic polymorphisms and childhood asthma susceptibility was evaluated by a pooled odds ratio with a 95% confidence interval.Results:In total, 14 case–control studies were included in the analysis. No significant association existed between risk of childhood asthma and the -403G/A polymorphism subjected to any genetic framework in the overall population. In the stratified analysis, according to ethnicity, the -403G/A polymorphism was linked to augmented vulnerability to childhood asthma in Caucasians (allelic model: odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.04–2.57,P = .034; codominant model: OR = 2.20, 95% CI = 1.28–3.78,P = .004; dominant model: OR = 1.78, 95% CI = 1.01–3.13,P = .047; and recessive model: OR = 1.92, 95% CI = 1.11–3.30,P = .019). For the stratified analysis by atopic status, the -403G/A polymorphism was linked to augmented childhood asthma in the codominant (OR = 1.39, 95% CI = 1.02–1.91,P = .037) and dominant models (OR = 1.43, 95% CI = 1.02–2.01,P = .037) in atopic asthma. For the -28C/G polymorphism, there was a significant association between childhood asthma and the -28C/G variant (allelic model: OR = 1.33, 95% CI = 1.08–1.65,P = .009; codominant framework: OR = 2.14, 95% CI = 1.47–3.10,P < .001; dominant model: OR = 1.44, 95% CI = 1.07–1.93,P = .017; and recessive model: OR = 2.08, 95% CI = 1.44–3.02,P < .001). Stratified analysis based on ethnicity and the -28C/G polymorphism was linked to augmented vulnerability to childhood asthma in Asian and Caucasian populations. For the subgroup analysis by atopic status, no association was found in atopic and non-atopic asthma.Conclusion:The present meta-analysis indicated that the RANTES -403G/A and -28C/G polymorphisms contributed to the development of childhood asthma.
A protocol of systematic review and meta-analysis of Mozart's Music for drug-resistant epilepsy
Authors: Wang Ke-Jian , Zhang Shi-Hua , Yu Jia-Nan , Sun Guang-Tao , Dong Shu-Xin 
Published: July 2020

Abstract

Background:
This study will aim to assess the effectiveness of Mozart's Music (MM) for the management of patients with drug-resistant epilepsy (DRE).

Methods:
In this study, we will search MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, Chinese Scientific Journal Database Information, WANGFANG, and China National Knowledge Infrastructure from their inauguration to March 1, 2020 without language and publication time restrictions. We will also identify other literature resources, such as reference lists of any related reviews. Trial quality will be examined by Cochrane risk of bias tool; reporting bias will be identified by a funnel plot and Egger test; and statistical analysis will be undertaken by RevMan 5.3 software.

Results:
This study will summarize high quality randomized controlled trials to appraise the effectiveness and safety of MM for the treatment of patients with DRE.

Conclusions:
The findings of this study will supply evidence to judge whether MM is effective on DRE at evidence-based medicine level.

Study registration number:
CRD42020170512.
CT imaging and pathological basis of linear shadow connecting pulmonary segmental artery to horizontal fissure
Authors: Guan Chun-Shuang , Yan Shuo , Lv Zhi-Bin , Sun Lei , Ma Da-Qing , Zhang Yan-Song , Xie Ru-Ming , Chen Bu-Dong 
Published: July 2020

Abstract
To investigate the computed tomography (CT) imaging and pathological basis of the linear shadows connecting pulmonary segmental arteries to horizontal fissure (hereinafter referred to as “linear shadow”) on thin-slice CT.
Collect 127 clinical cases to analyze the display and morphology of linear shadows on the thin-slice CT and to measure their length, thickness, and angle. Collect 11 autopsy specimens of coal worker's pneumoconiosis to conduct an imaging and pathology basis control study for the linear shadows.
There is no correlation between the linear shadow and gender, age, and smoking history. Linear shadows are observed in 54.33% of patients. 93.33% of those linear shadows are straight lines. Generally, the lengths are less than 10 mm, the thicknesses are around 1 mm, and the scopes of angles are wide, range from acute angles to obtuse angles. The linear shadow is a banded structure consisting of loose connective tissue, small blood vessels, and small lymphatic vessels due to the visceral pleura recessed and fused into the lung.
Linear shadows are intrinsic to the lung. The linear shadows consist of loose connective tissue, small blood vessels, and small lymphatic vessels.
COVID-19 national lockdown in Morocco: impacts on air quality and public health
Authors: Khomsi Kenza , Najmi Houda , Amghar Hassan , Chelhaoui Youssef , Souhaili Zineb 
Published: July 2020

AbstractOn the 20th April 2020, the end date of the first strict lockdown period in Morocco, 2 403 410 cases of the corona Virus were confirmed globally. The number of Morocco confirmed cases attended 2990, while 12 746 were suspected and 143 deaths were recorded. Due to the pandemic of coronavirus disease 2019 worldwide and in Morocco, almost all avoidable activities in the country were prohibited since the kingdom announced activities reduction on March 16, 2020 and then general lockdown with reduced industrial activities on March 20, 2020.This study aims at comparing the air quality status in Casablanca and Marrakech, two large cities from Morocco, before the pandemic and during the lockdown situation to show whether COVID-19 compelled-anthropogenic activities lockdown may have saved lives by restraining ambient air pollution than by preventing infection.We found that, during the quarantine, NO2 dropped by -12 μg/m3 in Casablanca and -7 μg/m3 in Marrakech. PM2·5 dropped by -18 μg/m3 in Casablanca and -14 μg/m3 in Marrakech. CO dropped by -0.04 mg/m3 in Casablanca and -0.12 mg/m3 in Marrakech. This air pollution reduction had created human health benefits and had reduced mortality and saved lives mainly from cardiovascular diseases.
Mass Generation, Neuron Labelling and 3D Imaging of Minibrains
Authors: Govindan Subashika , Batti Laura , Osterop Samira F , Stoppini Luc , Roux Adrien 
Published: July 2020

AbstractMinibrain is a sphericalin vitro3D brain organoid model, composed of a mixed population of neurons and glial cells, generated from human iPSC derived neural stem cells. Despite the advances in human brain organoid models, there is a lack of labelling and imaging methodologies to characterize these models. In this study, we present a step-by-step methodology to generate human minibrain nurseries and novel strategies to subsequently label projection neurons, perform immunohistochemistry and 3D imaging of the minibrains at large multiplexable scales. To visualize projection neurons, we adapt viral transduction and to visualize the organization of cell types we implement immunohistochemistry. To facilitate 3D imaging of minibrains, we present here pipelines and accessories for one step mounting and clearing suitable for confocal microscopy. The pipelines are specifically designed in such a way that the assays can be multiplexed with ease for large-scale screenings using minibrains. Using the pipeline, we present i. dendrite morphometric properties obtained from 3D neuron morphology reconstructions and ii. distribution and quantification of cell types in 3D across whole mount organoids.