bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
Authors: Van Vaerenbergh Inge , Adriaenssens Tom , Coucke Wim , Van Landuyt Lisbet , Verheyen Greta , De Brucker Michaël , Camus Michel , Platteau Peter , De Vos Michel , Van Hecke Elien , Rosenthal André , Smitz Johan 
Published: February 2021

Abstract
Background
Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only.

Methods
A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22–39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves.

Results
The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001).
Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3–4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3.

Conclusions
This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort.

Trial registration
Clinicaltrials.gov, NCT03659786/NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.
Small-molecule antagonist of VLA-4 (GW559090) attenuated neuro-inflammation by targeting Th17 cell trafficking across the blood-retinal barrier in experimental autoimmune uveitis
Authors: Chen Yi Hsing , Eskandarpour Malihe , Zhang Xiaozhe , Galatowicz Grazyna , Greenwood John , Lightman Sue , Calder Virginia 
Published: February 2021

Abstract
Background
The integrin VLA-4 (α4β1) plays an important role in leukocyte trafficking. This study investigated the efficacy of a novel topical α4β1 integrin inhibitor (GW559090, GW) in a mouse model for non-infectious posterior uveitis (experimental autoimmune uveitis; EAU) and its effect on intraocular leukocyte subsets.

Methods
Mice (female; B10.RIII or C57Bl/6; aged 6–8 weeks) were immunized with specific interphotoreceptor retinoid-binding protein (IRBP) peptides to induce EAU. Topically administered GW (3, 10, and 30 mg/ml) were given twice daily either therapeutically once disease was evident, or prophylactically, and compared with vehicle-treated (Veh) and 0.1% dexamethasone-treated (Dex) controls. Mice were sacrificed at peak disease. The retinal T cell subsets were investigated by immunohistochemistry and immunofluorescence staining. The immune cells within the retina, blood, and draining lymph nodes (dLNs) were phenotyped by flow cytometry. The effect of GW559090 on non-adherent, adherent, and migrated CD4+ T cell subsets across a central nervous system (CNS) endothelium was further assayed in vitro and quantitated by flow cytometry.

Results
There was a significant reduction in clinical and histological scores in GW10- and Dex-treated groups as compared to controls either administered therapeutically or prophylactically. There were fewer CD45+ leukocytes infiltrating the retinae and vitreous fluids in the treated GW10 group (P < 0.05). Immunofluorescence staining and flow cytometry data identified decreased levels of retinal Th17 cells (P ≤ 0.001) in the GW10-treated eyes, leaving systemic T cell subsets unaffected. In addition, fewer Ly6C+ inflammatory monocyte/macrophages (P = 0.002) and dendritic cells (P = 0.017) crossed the BRB following GW10 treatment. In vitro migration assays confirmed that Th17 cells were selectively suppressed by GW559090 in adhering to endothelial monolayers.

Conclusions
This α4β1 integrin inhibitor may exert a modulatory effect in EAU progression by selectively blocking Th17 cell migration across the blood-retinal barrier without affecting systemic CD4+ T cell subsets. Local α4β1 integrin-directed inhibition could be clinically relevant in treating a Th17-dominant form of uveitis.
Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation
Authors: He Jia-Hui , Liu Rong-Pei , Peng Yi-Man , Guo Qing , Zhu Lan-Bing , Lian Yi-Zhi , Hu Bei-Lei , Fan Hui-Hui , Zhang Xiong , Zhu Jian-Hong 
Published: February 2021

Abstract
Background
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants.

Methods
Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed.

Results
All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1β (IL-1β). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1β but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity.

Conclusions
The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.
Assessing knowledge, attitudes, and practice of health providers towards the provision of postpartum intrauterine devices in Nepal: a two-year follow-up
Authors: Stone Lucy , Puri Mahesh C. , Guo Muqi , Shah Iqbal H. 
Published: February 2021

Abstract
Background
Health service providers play a key role in addressing women’s need for postpartum pregnancy prevention. Yet, in Nepal, little is known about providers’ knowledge, attitudes, and practice (KAP) on providing postpartum family planning (PPFP), particularly the immediate postpartum intrauterine device (PPIUD). This paper assesses providers KAP towards the provision of PPIUDs in Nepal prior to a PPIUD intervention to gain a baseline insight and analyzes whether their KAP changes both 6 and 24 months after the start of the intervention.

Methods
Data come from a randomized trial assessing the impact of a PPIUD intervention in Nepal between 2015 and 2017. We interviewed 96 providers working in six study hospitals who completed a baseline interview and follow-up interviews at 6 and 24 months. We used descriptive analysis, McNemar’s test and the Wilcoxon signed-rank test to assess KAP of providers over 2 years.

Results
The PPIUD KAP scores improved significantly between the baseline and 6-month follow-up. Knowledge scores increased from 2.9 out of 4 to 3.5, attitude scores increased from 4 out of 7 to 5.3, and practice scores increased from 0.9 out of 3 to 2.8. There was a significant increase in positive attitude and practice between 6 and 24 months. Knowledge on a women’s chance of getting pregnant while using an IUD was poor. Attitudes on recommending a PPIUD to different women significantly improved, however, attitudes towards recommending a PPIUD to unmarried women and women who have had an ectopic pregnancy improved the least. Practice of PPIUD counseling and insertion improved significantly from baseline to 24 months, from 10.4 and 9.4% to 99% respectively.

Conclusions
Although KAP improved significantly among providers during the PPIUD intervention, providers’ knowledge on a women’s chance of getting pregnant while using an IUD and attitudes towards recommending a PPIUD to unmarried women and women who have had an ectopic pregnancy improved the least. Provider KAP could be improved further through ongoing and more in-depth training to maintain providers’ knowledge, reduce provider bias and misconceptions about PPIUD eligibility, and to ensure providers understand the importance of birth spacing.
The effect of women’s body mass index on pelvic organ prolapse: a systematic review and meta analysis
Authors: Zenebe Chernet Baye , Chanie Wagaye Fentahun , Aregawi Aster Berhe , Andargie Tamiru Minwuye , Mihret Muhabaw Shumye 
Published: February 2021

Abstract
Background
Pelvic organ prolapse remains the public health challenge globally. Existing evidences report the effect of woman’s weight on the pelvic organ prolapse inconsistently and this urges the need of pooled body weight effect on the pelvic organ prolapse. Although there was a previous work on this regard, it included papers reported before June 18/2015. Thus, updated and comprehensive evidence in this aspect is essential to devise strategies for interventions.

Objective
This review aimed at synthesizing evidence regarding the pooled effect of body weight on the pelvic organ prolapsed.

Methods
For this review, we searched all available articles through databases including PubMed, Web of Sciences, CINAHL, JBI library, Cochran library, PsycInfo and EMBASE as well as grey literature including Mednar, worldwide science, PschEXTRA and Google scholar. We included cohort, case–control, cross-sectional and experimental studies which had been reported between March 30, 2005 to March 30, 2020. In the effect analysis, we utilized random model. The heterogeneity of the studies was determined by I2 statistic and the publication bias was checked by Egger’s regression test. Searching was limited to studies reported in the English language.

Results
A total of 14 articles with 53,797 study participants were included in this systematic review (SR) and meta analysis (MA). The pooled result of this Meta analyses depict that body mass index (BMI) doesn’t have statistical significant association with pelvic organ prolapse.

Conclusion
This review point out that women’s body mass index has no significant effect on the development of pelvic organ prolapse. However, the readers should interpret the result with cautions due to the presence of considerable limitations in this work.
Trial registration The protocol of this systematic review (SR) and meta analysis (MA) has been registered in PROSPERO databases with the Registration number of CRD42020186951
FOPR test: a virtual reality-based technique to assess field of perception and field of regard in hemispatial neglect
Authors: Kim Tae-Lim , Kim Kwanguk , Choi Changyeol , Lee Ji-Yeong , Shin Joon-Ho 
Published: February 2021

Abstract
Background
We previously proposed a novel virtual reality-based method to assess human field of perception (FOP) and field of regard (FOR), termed the FOPR test. This study assessed the diagnostic validity of the FOPR test for hemispatial neglect (HSN).

Methods
We included 19 stroke patients with a lesion in the right hemisphere and with HSN (HSN+SS), 22 stroke patients with a lesion in the right hemisphere and without HSN (HSN−SS), and 22 healthy controls aged 19–65 years. The success rate (SR) and response time (RT) in the FOPR test for both FOP and FOR were assessed (FOP-SR, FOR-SR, FOP-RT, and FOR-RT, respectively). Using a Bland–Altman plot, agreements between the FOPR test and conventional tests were confirmed, and the FOPR test accuracy was verified using the support vector machine (SVM). Measured values were analysed using ANOVA and Kruskall–Wallis tests for group comparison.

Results
The Bland–Altman plot showed good agreement between FOPR test and conventional tests; individuals within 95% agreement limits were within the range of 94.8–100.0%. The SVM classification accuracy, using FOP and FOR variables from the left hemispace, ranged from 83.3 to 100.0% in a binary classification (HSN vs non-HSN). The FOPR test demonstrated differences in SR and RT for both FOP and FOR across the groups.

Conclusion
The FOPR test was valid for the HSN diagnosis and provided quantitative and intuitive information regarding visuospatial function. Furthermore, it might enhance our understanding of visuospatial function including HSN by applying the time relative component and concepts of perception and exploration, FOP and FOR.
Trial registration: NCT03463122. Registered 13 March 2018, retrospectively registered.
Epidemiology and genotypic diversity of human metapneumovirus in paediatric patients with acute respiratory infection in Beijing, China
Authors: Wang Chao , Wei Tianli , Ma Fenlian , Wang Hao , Guo Jianqiang , Chen Aijun , Huang Yiman , Xie Zhiping , Zheng Lishu 
Published: February 2021

Abstract
Background
Acute respiratory tract infections (ARTIs) causes high amounts of morbidity and mortality worldwide every year. Human metapneumovirus (HMPV) is a major pathogen of ARTIs in children. In this study, we aimed to investigate the epidemiology and genotypic diversity of HMPV in children hospitalized with ARTIs in Beijing, China.

Methods
Hospitalized children aged < 14 years with ARTIs were enrolled from April 2017 to March 2018; nasopharyngeal aspirates were collected and subjected to real-time polymerase chain reaction tests for HMPV. HMPV-positive samples were genotyped based on a partial N gene. Whole genome sequences were determined for samples with high viral loads.

Results
4.08% (52/1276) enrolled paediatric patients were identified as having HMPV infection. The epidemic season is winter and early spring, children aged ≤ 4 years were more susceptible to HMPV infection (47/52, 90.38%). The co-infection rate were 36.54% (19/52), the most common co-infected virus were influenza and respiratory syncytial virus. The main diagnoses of HMPV infection were pneumonia (29/52, 55.77%) and bronchitis (23/52, 44.23%), while the main clinical manifestations were cough, fever, rhinorrhoea, and sneeze. Among 48 HMPV-positive specimens, A2b (19/48, 39.58%) and B1 (26/48, 54.17%) were the main epidemic subtypes. Patients with HMPV genotype A infection had a higher viral load compared to genotype B patients (6.07 vs. 5.37 log10 RNA copies/ml). Five complete sequences of HMPV were obtained. This is the first report of a whole genome sequence of HMPV-B1 isolated in China.

Conclusions
HMPV is an important respiratory pathogen in paediatric patients. Cases of HMPV infection could burden hospitals in the epidemic season. HMPV viral loads and genotypes have no correlation with co-infection or clinical characteristics.
Lotus leaf extract inhibits ER− breast cancer cell migration and metastasis
Authors: Tong Yuelin , Li Zhongwei , Wu Yikuan , Zhu Shenglong , Lu Keke , He Zhao 
Published: February 2021

Abstract
Background
Patients with estrogen receptor negative (ER−) breast cancer have poor prognosis due to high rates of metastasis. However, there is no effective treatment and drugs for ER− breast cancer metastasis. Our purpose of this study was to evaluate the effect of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER− breast cancer.

Methods
The anti-migratory effect of LAE were analyzed in ER− breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806 cell lines. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were used to evaluate the cytotoxicity and anti-migratory effect of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo, subcutaneous xenograft and intravenous injection nude mice models were established. Lung and liver tissues were analyzed by the hematoxylin and eosin staining and immunoblotting assay.

Results
We found that lotus LAE, not nuciferine, inhibited cell migration significantly in SK-BR-3, MDA-MB-231 and HCC1806 breast cancer cells, and did not affect viability of breast cancer cells. The anti-migratory effect of LAE was dependent on TGF-β1 signaling, while independent of Wnt signaling and autophagy influx. Intracellular H2O2 was involved in the TGF-β1-related inhibition of cell migration. LAE inhibited significantly the breast cancer cells metastasis in mice models. RNA-sequence analysis showed that extracellular matrix signaling pathways are associated with LAE-suppressed cell migration.

Conclusions
Our findings demonstrated that lotus leaf alcohol extract inhibits the cell migration and metastasis of ER− breast cancer, at least in part, via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling pathways, which provides a potential therapeutic strategy for ER− breast cancer.
Fat mass to fat-free mass ratio and the risk of non-alcoholic fatty liver disease and fibrosis in non-obese and obese individuals
Authors: Dai Huajie , Xiang Jiali , Hou Yanan , Xuan Liping , Wang Tiange , Li Mian , Zhao Zhiyun , Xu Yu , Lu Jieli , Chen Yuhong , Wang Weiqing , Ning Guang , Bi Yufang , Xu Min 
Published: February 2021

Abstract
Context
Body composition may explain partially why non-obese individuals still at the risk of developing non-alcoholic fatty liver disease (NAFLD). The ratio of fat mass to fat-free mass (FM/FFM) has been proposed to assess the combined effect of different body compositions.

Objective
We aimed to investigate the associations of FM/FFM ratio with the risk of developing NAFLD and fibrosis and to identify the potential mediators according to obesity status.

Methods
This cohort study comprised 3419 adults age ≥ 40 years and free of NAFLD at baseline. Body composition was measured by bioelectrical impedance analysis. NAFLD was ascertained by ultrasonography and fibrosis was assessed by non-invasive score systems.

Results
For each 1 standard deviation increment in FM/FFM ratio, the odds ratio for the risk of NAFLD was 1.55 (95% confidence interval [CI] 1.23–1.95) in non-obese men, 1.33 (95% CI 1.08–1.65) in obese men, 1.42 (95% CI 1.44–1.67) in non-obese women, and 1.29 (95% CI 1.12–1.50) in obese women. Similar associations were also found between FM/FFM ratio and NAFLD with fibrosis. Mediation analysis showed that insulin resistance, triglycerides, high-density lipoprotein cholesterol, white blood cells, and total cholesterol mediated the association of FM/FFM ratio with NAFLD risk in specific sex and obesity subgroups.

Conclusions
The FM/FFM ratio significantly associated with the NAFLD and fibrosis risk in both non-obese and obese individuals. Different factors may mediate the association between body composition and NAFLD risk according to different obesity status.
Femtosecond pulsed laser microscopy: a new tool to assess the in vitro delivered dose of carbon nanotubes in cell culture experiments
Authors: Lison Dominique , Ibouraadaten Saloua , van den Brule Sybille , Todea Milica , Vulpoi Adriana , Turcu Flaviu , Ziemann Christina , Creutzenberg Otto , Bonner James C. , Ameloot Marcel , Bové Hannelore 
Published: February 2021

Abstract
Background
In vitro models are widely used in nanotoxicology. In these assays, a careful documentation of the fraction of nanomaterials that reaches the cells, i.e. the in vitro delivered dose, is a critical element for the interpretation of the data. The in vitro delivered dose can be measured by quantifying the amount of material in contact with the cells, or can be estimated by applying particokinetic models. For carbon nanotubes (CNTs), the determination of the in vitro delivered dose is not evident because their quantification in biological matrices is difficult, and particokinetic models are not adapted to high aspect ratio materials. Here, we applied a rapid and direct approach, based on femtosecond pulsed laser microscopy (FPLM), to assess the in vitro delivered dose of multi-walled CNTs (MWCNTs).

Methods and results
We incubated mouse lung fibroblasts (MLg) and differentiated human monocytic cells (THP-1) in 96-well plates for 24 h with a set of different MWCNTs. The cytotoxic response to the MWCNTs was evaluated using the WST-1 assay in both cell lines, and the pro-inflammatory response was determined by measuring the release of IL-1β by THP-1 cells. Contrasting cell responses were observed across the MWCNTs. The sedimentation rate of the different MWCNTs was assessed by monitoring turbidity decay with time in cell culture medium. These turbidity measurements revealed some differences among the MWCNT samples which, however, did not parallel the contrasting cell responses. FPLM measurements in cell culture wells revealed that the in vitro delivered MWCNT dose did not parallel sedimentation data, and suggested that cultured cells contributed to set up the delivered dose. The FPLM data allowed, for each MWCNT sample, an adjustment of the measured cytotoxicity and IL-1β responses to the delivered doses. This adjusted in vitro activity led to another toxicity ranking of the MWCNT samples as compared to the unadjusted activities. In macrophages, this adjusted ranking was consistent with existing knowledge on the impact of surface MWCNT functionalization on cytotoxicity, and might better reflect the intrinsic activity of the MWCNT samples.

Conclusion
The present study further highlights the need to estimate the in vitro delivered dose in cell culture experiments with nanomaterials. The FPLM measurement of the in vitro delivered dose of MWCNTs can enrich experimental results, and may refine our understanding of their interactions with cells.