bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined cART including Tenofovir Disoproxil, Emtricitabine, and Dolutegravir has potent therapeutic effects in HIV-1 infected humanized mice
Authors: Weichseldorfer Matthew , Affram Yvonne , Heredia Alonso , Rikhtegaran-Tehrani Zahra , Sajadi Mohammad M. , Williams Sumiko P. , Tagaya Yutaka , Benedetti Francesca , Ramadhani Habib O. , Denaro Frank , Munawwar Arshi , Bryant Joseph , Zella Davide , Reitz Marvin , Romerio Fabio , Latinovic Olga S. 
Published: October 2021

AbstractHIV-1 reservoirs persist in the presence of combined antiretroviral therapy (cART). However, cART has transformed HIV-1 infection into a chronic disease marked by control of HIV-1 viral load and mortality reduction. Major challenges remain, including viral resistance upon termination of cART and persistence and identification of tissue distribution of HIV-1 reservoirs. Thus, appropriate animal models that best mimic HIV-1 pathogenesis are important, and the current study complements our previously published validation of the CD34+ hematopoietic humanized mouse model for this purpose. Here we analyze viral suppression using the recently developed combination of antiretrovirals that include Tenofovir Disoproxil (TDF), Emtricitabine (FTC), and Dolutegravir (DTG), a choice based on recent clinical outcomes showing its improved antiretroviral potency, CD4+ T cell preservation, tolerability, and prevention of viral drug resistance compared to that of previous regimens. We used quantitative Airyscan-based super resolution confocal microscopy of selected mouse tissues. Our data allowed us to identify specific solid tissue reservoirs of human T cells expressing the HIV-1 core protein p24. In particular, lymph node, brain, spleen, and liver were visualized as reservoirs for residual infected cells. Marked reduction of viral replication was evident. Considering that detection and visualization of cryptic sites of HIV-1 infection in tissues are clearly crucial steps towards HIV-1 eradication, appropriate animal models with pseudo-human immune systems are needed. In fact, current studies with humans and non-human primates have limited sample availability at multiple stages of infection and cannot easily analyze the effects of differently administered combined antiretroviral treatments on multiple tissues. That is easier to manage when working with humanized mouse models, although we realize the limitations due to low human cell recovery and thus the number of cells available for thorough and comprehensive analyses. Nonetheless, our data further confirm that the CD34+ humanized mouse model is a potentially useful pre-clinical model to study and improve current anti-HIV-1 therapies.
A case report of a severe neonatal systemic vasculitis on the first day of life
Authors: Wong Stephanie , Demirkaya Erkan , Berard Roberta 
Published: October 2021

Abstract
Background
Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren’s syndrome, Behҫet’s disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate.

Case presentation
In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred.
He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy.
The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development.

Conclusion
This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.
Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Authors: Cui Yu , Zhang Zhaolong , Zhou Xin , Zhao Zhiyuan , Zhao Rui , Xu Xiangyu , Kong Xiangyi , Ren Jinyang , Yao Xujin , Wen Qian , Guo Feifei , Gao Shengli , Sun Jiangdong , Wan Qi 
Published: October 2021

Abstracts
Background
Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis.

Methods
Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions.

Results
We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions.

Conclusions
These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.
T-cell dysregulation is associated with disease severity in Parkinson’s Disease
Authors: Bhatia Divisha , Grozdanov Veselin , Ruf Wolfgang P. , Kassubek Jan , Ludolph Albert C. , Weishaupt Jochen H. , Danzer Karin M. 
Published: October 2021

AbstractThe dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemagglutinin that also correlated with disease severity. In summary, our data suggest that the consequences of disease severity account for the changes in PD T cells, rather than age, age of onset, duration or the disease progression rate.
Comparability of family planning quality of care measurement tools in low-and-middle income country settings: a systematic review
Authors: Hazel Elizabeth , Mohan Diwakar , Gross Margaret , Kattinakere Sreedhara Sushama , Shrestha Prakriti , Johnstone Maia , Marx Melissa 
Published: October 2021

Abstract
Background
In low-and-middle income countries (LMICs), accurate measures of the elements of quality care provided by a health worker through family planning services (also known as process quality) are required to ensure family’s contraceptives needs are being met. There are many tools used to assess family planning process quality of care (QoC) but no one standardized method. Those measuring QoC in LMICs should select an appropriate tool based the program context and financial/logistical parameters, but they require data on how well each tool measures routine clinical care. We aim to synthesize the literature on validity/comparability of family planning process QoC measurement tools through a quantitative systematic review with no meta-analysis.

Methods
We searched six literature databases for studies that compared quality measurements from different tools using quantitative statistics such as sensitivity/specificity, kappa statistic or absolute difference. We extracted the comparative measure along with other relevant study information, organized by quality indicator domain (e.g. counseling and privacy), and then classified the measure by low, medium, and high agreement.

Results
We screened 8172 articles and identified eight for analysis. Studies comparing quality measurements from simulated clients, direct observation, client exit interview, provider knowledge quizzes, and medical record review were included. These eight studies were heterogenous in their methods and the measurements compared. There was insufficient data to estimate overall summary measures of validity for the tools. Client exit interviews compared to direct observation or simulated client protocols had the most data and they were a poor proxy of the actual quality care received for many measurements.

Conclusion
To measure QoC consistently and accurately in LMICs, standardized tools and measures are needed along with an established method of combining them for a comprehensive picture of quality care. Data on how different tools proxy quality client care will inform these guidelines. Despite the small number of studies found during the review, we described important differences on how tools measure quality of care.
Decomposing the urban–rural inequalities in the utilisation of maternal health care services: evidence from 27 selected countries in Sub-Saharan Africa
Authors: Samuel Oduse , Zewotir Temesgen , North Delia 
Published: October 2021

Abstract
Background
There has been a substantial improvement in reducing maternal mortality in the Sub-Saharan African region. The vast rural-urban gap in maternal health outcomes, however, is obscured by this average achievement. This study attempts to measure the contribution of identified risk factors to describe the average rural-urban difference in the use of antenatal care, health facilities for delivery, and health professional assistance at delivery.

Method
To achieve this objective, we used descriptive analysis and Fairlie non-linear decomposition method to quantify covariates’ contribution in explaining the urban–rural difference in maternal healthcare services utilisation.

Result
The study’s finding shows much difference between urban and rural areas in the use of maternal healthcare services. Socio-economic factors such as household wealth index, exposure to media, and educational level of women and their husbands/partners contributed the most in explaining the gap between urban and rural areas in healthcare services utilisation.

Conclusions
Interventions to bridge the gap between urban and rural areas in maternal healthcare services utilisation in Sub-Saharan Africa should be centred towards socio-economic empowerment. Government can enforce targeted awareness campaigns to encourage women in rural communities in Sub-Sharan Africa to take the opportunity and use the available maternal health care services to be at par with their counterparts in urban areas.
Human cytomegalovirus inhibits the proliferation and invasion of extravillous cytotrophoblasts via Hippo-YAP pathway
Authors: Kong Qiaoqiao , Li Jing , Zhao Li , Shi Peng , Liu Xiaobei , Bian Cailing , Liu Jing , Liu Tao 
Published: October 2021

Abstract
Background
Human cytomegalovirus (HCMV) infection in utero is very common during pregnancy, which can lead to adverse outcomes in both pregnancy and progeny, but its pathogenesis has not been fully clarified. The decrease of extravillous cytotrophoblasts (EVT) invasion is an essential pathophysiological process of some pregnancy complications. Hippo-YAP signaling pathway plays an important role in regulating cell proliferation and apoptosis. However, whether YAP is involved in HCMV uterine infection remains to be studied.

Methods
The primary EVT was cultured and infected by the HCMV strain AD169 virus in vitro. Immunofluorescence staining of HCMVpp65 antigen was conducted afterward to confirm the establishment of an infection model. The optimal virus infection dose was determined by the EVT proliferation status in vitro. Real-time PCR was performed to examine the mRNA level of major genes involved in the Hippo pathway in EVT after HCMV infection. The effect of HCMV on the expression of YAP protein in EVT was evaluated by Immunofluorescence staining and Western blot. An in vitro cell invasion assay was carried out to analyze the influence of HCMV on EVT invasion. The changes of EVT invasion was accessed by establishing YAP silencing and over-expression models using YAP1 specific siRNA and plasmid pcDH.

Results
The optimal HCMV infection dose was 282.5TCID50/ml. Compared to the control group, the infection of HCMV significantly reduced the mRNA expression of Mst1, Mst2, SAV, Lats1, Lats2, Mob1, YAP1, TAZ, TEAD1-4 genes and YAP protein expression in the Hippo-YAP pathway. HCMV infection also decreased the EVT invasion. In non-infected EVT, the number of transmembrane EVT cells was significantly reduced when YAP1 gene was silenced, while it was significantly increased when YAP1 gene was over-expressed. In the HCMV-infected EVT, the number of transmembrane EVT cells significantly increased when over-expressed and eventually recovered to the level of NC.

Conclusions
HCMV may decrease EVT invasion by inhibiting the expression of mRNA and protein of YAP in the Hippo-YAP signaling pathway. HCMV eventually reduces the invasion ability of EVT by inhibiting multiple genes in the Hippo-YAP signaling pathway, especially inhibiting YAP which serves as the downstream effector.
Dietary curcumin supplementation promotes browning and energy expenditure in postnatal overfed rats
Authors: Zhu Xiaolei , Du Susu , Yan Qinhui , Min Cuiting , Zhou Nan , Zhou Wei , Li Xiaonan 
Published: October 2021

Abstract
Background
Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats.

Methods and results
This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.

Conclusion
Dietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.
Prevalence of exclusive breastfeeding practice and its association with maternal employment in Ethiopia: a systematic review and meta-analysis
Authors: Wake Getu Engida , Mittiku Yohannes Moges 
Published: October 2021

AbstractBackgroundExclusive breastfeeding is defined as the practice of providing only breast milk for an infant for the first 6 months of life without the addition of any other food or water, except for vitamins, mineral supplements, and medicines. Findings are inconsistent regarding the prevalence of exclusive breastfeeding in Ethiopia. Full-time maternal employment is an important factor contributing to the low rates of practice of exclusive breastfeeding. Empowering women to exclusively breastfeed, by enacting 6 months’ mandatory paid maternity leave can increase the rate of exclusive breastfeeding in the first 6 months of life up to 50%. The purpose of this review was to estimate the pooled prevalence of exclusive breastfeeding and its association with full-time maternal employment in the first 6 months of life for infants in the context of Ethiopia.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in this systematic review and meta-analysis. All observational studies reporting the prevalence of exclusive breastfeeding and its association with maternal employment in Ethiopia were considered. The search was conducted from 6 November 2020 to 31 December 2020 and all papers published in the English language from 1 January 2015 to 31 December 2020 were included in this review.ResultsForty-five studies were included in the final analysis after reviewing 751 studies in this meta-analysis yielding the pooled prevalence of EBF 60.42% (95% CI 55.81, 65.02) at 6 months in Ethiopia. Those full-time employed mothers in the first 6 months were 57% less likely to practice exclusive breastfeeding in comparison to mothers not in paid employment in Ethiopia (OR 0.43; 95% CI 0.31, 0.61).ConclusionsFull-time maternal employment was negatively associated with the practice of exclusive breastfeeding in comparison to unemployed mothers. The prevalence of exclusive breastfeeding in Ethiopia is low in comparison to the global recommendation. The Ethiopian government should implement policies that empower women. The governmental and non-governmental organizations should create a conducive environment for mothers to practice exclusive breastfeeding in the workplace.
Experimental study on creep properties prediction of reed bales based on SVR and MLP
Authors: Li Jixia , Zhang Lixin , Huang Guangdi , Wang Huan , Jiang Youzhong 
Published: October 2021

AbstractBackgroundReed has high lignin content, wide distribution and low cost. It is an ideal raw material for replacing wood in the paper industry. Reeds are rich in resources, but the density of reeds is low, leading to high transportation and storage costs. This paper aims to study the compression process of reeds and the creep behaviour of compressed reeds, and provide theoretical guidance for the reed compressor management, bundling equipment and the stability of compressed reed bales.ResultsWe have established a multi-layer perceptron network prediction model for the creep characteristics of reeds, and the prediction rate R2of this model is greater than 0.997. The constitutive equation, constitutive coefficient and creep quaternary model of the reed creep process were established by using the prediction model. The creep behaviour of the reed bale is positively correlated with the initial maximum compressive stress (σ0). During the creep of the reed, the elastic power and the viscous resistance restrict each other. The results show that the proportion of elastic strain in the initial stage is the largest, and gradually decreases to 99.19% over time. The viscoelastic strain increases rapidly with time, then slowly increases, and finally stabilizes to 0.69%, while the plastic strain accounts for the proportion of the total strain. The specific gravity of the reed increases linearly with the increase of creep time, and finally accounts for 0.39%, indicating that as time increases, the damage of the reed's own structure gradually increases.ConclusionsWe studied the relationship between the strain and time of the reed and the strain and creep behaviour of the reed bag under different holding forces under constant force. It is proved that the multi-layer perceptron network is better than the support vector machine regression in predicting the characteristics of reed materials. The three stages of elasticity, viscoelasticity and plasticity in the process of reed creep are analysed in detail. This article opens up a new way for using machine learning methods to predict the mechanical properties of materials. The proposed prediction model provides new ideas for the characterization of material characteristics.