bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated costs for the delivery of safer conception strategies for HIV-discordant couples in Zimbabwe: a cost analysis
Authors: Hughes Carolyn Smith , Brown Joelle , Murombedzi Caroline , Chirenda Thandiwe , Chareka Gift , Mhlanga Felix , Mateveke Bismark , Gitome Serah , Makurumure Tinei , Matubu Allen , Mgodi Nyaradzo , Chirenje Zvavahera , Kahn James G. 
Published: October 2020

Abstract
Background
In recent years, safer conception strategies have been developed to help HIV-serodiscordant couples conceive a child without transmitting HIV to the seronegative partner. The SAFER clinical trial assessed implementation of these strategies in Zimbabwe.

Methods
As a part of the SAFER study, we estimated the costs (in 2017 $US) associated with individual and combination strategies, in the trial setting and real-world practice, from a healthcare system perspective. Safer conception strategies included: 1) ART with frequent viral load testing until achieving undetectable viral load (ART-VL); 2) daily oral pre-exposure prophylaxis (PrEP); 3) semen-washing with intrauterine insemination; and 4) manual self-insemination at home. For costs in the trial, we used a micro-costing approach, including a time and motion study to quantify personnel effort, and estimated the cost per couple for individual and combination strategies for a mean of 6 months of safer services. For real-world practice, we modeled costs for three implementation scenarios, representing differences from the trial in input prices (paid by the Ministry of Health and Child Care [MOHCC]), intervention intensity, and increments to current HIV prevention and treatment practices and guidelines. We used one-way sensitivity analyses to assess the impact of uncertainty in input variables.

Results
Individual strategy costs were $769–$1615 per couple in the trial; $185–$563 if using MOHCC prices. Under the target intervention intensity and using MOHCC prices, individual strategy costs were $73–$360 per couple over and above the cost of current HIV clinical practices. The cost of delivering the most commonly selected combination, ART-VL plus PrEP, ranged from $166–$517 per couple under the three real-world scenarios. Highest costs were for personnel, lab tests, and strategy-specific consumables, in variable proportions by clinical strategy and analysis scenario. Total costs were most affected by uncertainty in the price of PrEP, number of semen-washing attempts, and scale-up of semen-washing capacity.

Conclusions
Safer conception methods have costs that may be affordable in many low-resource settings. These cost data will help implementers and policymakers add safer conception services. Cost-effectiveness analysis is needed to assess value for money for safer conception services overall and for safer strategy combinations.

Trial registration
Registry Name: Clinicaltrials.gov. Trial registration number: NCT03049176. Registration date: February 9, 2017.
Blood pressure and mortality in patients with type 2 diabetes and a recent coronary event in the ELIXA trial
Authors: Wijkman Magnus O. , Claggett Brian , Diaz Rafael , Gerstein Hertzel C. , Køber Lars , Lewis Eldrin , Maggioni Aldo P. , Wolsk Emil , Aguilar David , Bentley-Lewis Rhonda , McMurray John J. , Probstfield Jeffrey , Riddle Matthew , Tardif Jean-Claude , Solomon Scott D. , Pfeffer Marc A. 
Published: October 2020

Abstract
Background
The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure.

Methods
We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization.

Results
Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10 mmHg lower SBP 1.05 (95% CI 0.99–1.12) P = 0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13 (95% CI 1.04–1.22) P = 0.002) in 2325 patients with additional CVD (index ACS+ at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10 mmHg lower SBP 0.95 (0.86–1.04) P = 0.26; P for interaction 0.005).

Conclusions
The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration.
Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010
miR-21 regulates immunosuppression mediated by myeloid-derived suppressor cells by impairing RUNX1-YAP interaction in lung cancer
Authors: Meng Guangping , Wei Jinying , Wang Yanjun , Qu Danhua , Zhang Jie 
Published: October 2020

Abstract
Background
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer.

Methods
The proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-β, and GM-CSF in mouse serum were determined by ELISA. miR-21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays.

Results
MiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-β and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP.

Conclusions
Taken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development.
Prognostic value of systemic immune-inflammation index in patients with urologic cancers: a meta-analysis
Authors: Huang Yilong , Gao Yunfeng , Wu Yushen , Lin Huapeng 
Published: October 2020

AbstractBackgroundSeveral studies have reported that the systemic immune-inflammation index (SII) is associated with the prognosis of patients with urologic cancers (UCs). The aim of this study was to systematically evaluate the prognostic value of SII in UC patients.MethodsWe searched public databases for relevant published studies on the prognostic value of SII in UC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled to assess the relationships between SII and overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), overall response rate (ORR) and disease control rate (DCR).ResultsA total of 14 studies with 3074 patients were included. From the pooled results, we found that high SII was associated with worse overall survival (OS) in patients with UC (HR 2.58, 95% CI 1.59–4.21). Patients with high SII values also had poorer PFS (HR 1.92, 95% CI 1.29–2.88) and CSS (HR 2.58, 95% CI 1.36–4.91) as well as lower ORRs (HR 0.40, 95% CI 0.22–0.71) than patients with low SII values. In addition, the subgroup analysis of OS and PFS showed that the prognosis of patients with high SII was worse than that of patients with low SII.ConclusionsSII might be a promising noninvasive predictor in patients with UC. However, more samples and multicenter studies are needed to confirm the effectiveness of SII in predicting the prognosis of patients with UC.
E2F1/2/7/8 as independent indicators of survival in patients with cervical squamous cell carcinoma
Authors: Yang Chang , Zhang Zhao-Cong , Liu Tian -Bo , Xu Ye , Xia Bai-Rong , Lou Ge 
Published: October 2020

Abstract
Background
Cervical cancer is the second leading cause of death in women 20–39 years old. Because coverage for cervical cancer screening is low, and the vaccination rate of human papillomavirus (HPV) is poor in some countries, potential markers to detect the disease at early stages are needed. E2F transcription factors (E2Fs) are a family of transcription factors that function in cell proliferation, differentiation, apoptosis, and tumorigenesis. As abnormal activation and regulation of E2Fs are related to tumor development and poor prognosis, we performed bioinformatic analyses and in vitro assays to evaluate the role of E2Fs in cervical cancer.

Methods
Transcriptional expression of E2Fs was initially evaluated in silico using ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA), followed by evaluation of E2F1/2/7/8 protein levels using immunohistochemistry in 88 patient tissues. E2F2 and E2F7 mRNA levels were measured by RT-qPCR. LinkedOmics and Metascape were used to predict functions of E2Fs, and in vitro experiments were performed to assess the tumorigenic role of E2F2 and E2F7.

Results
In silico analysis showed that E2F1/2/7/8 were significantly overexpressed in cervical cancer, findings which were confirmed at the protein level using immunohistochemistry. Further, upregulation of E2F1/2/7/8 was associated with different clinicopathological prognostic factors, including positivity for lymph vessel invasion and deep invasion of cervical stroma. Increased expression of E2F1/2/7/8 was also related to shorter overall survival (OS) and disease-free survival (DFS) in patients with cervical cancer. Using multivariate analysis, we confirmed E2F1/2/7/8 as independent prognostic factors for shorter OS of patients with cervical cancer. Finally, in vitro experiments showed that E2F2 and E2F7 are involved in cell proliferation and migration and cell cycle regulation in both HPV-positive and HPV-negative cervical cancer cells.

Conclusions
E2F1/2/7/8 may be prognostic biomarkers for survival of patients with cervical cancer. E2F2 and E2F7 are involved in cell proliferation, migration, and cell cycle in both HPV-positive and HPV-negative cervical cancer cells.
SLC2A3 promotes macrophage infiltration by glycolysis reprogramming in gastric cancer
Authors: Yao Xingxing , He Zhanke , Qin Caolitao , Deng Xiangqian , Bai Lan , Li Guoxin , Shi Jiaolong 
Published: October 2020

Abstract
Background
Tumors display a high rate of glucose metabolism and the SLC2A (also known as GLUT) gene family may be central regulators of cellular glucose uptake. However, roles of SLC2A family in mechanism of metabolite communication with immunity in gastric cancer remains unknown.

Methods
Bioinformatics analysis and IHC staining were used to reveal the expression of SLC2A3 in gastric cancer and the correlation with survival prognosis. Real-time PCR, western blots, OCR, ECAR, lactate production and glucose uptake assays were applied to determine the effect of SLC2A3 on glycolysis reprogramming. We then investigated the consequences of SLC2A3 upregulation or inhibition on aerobic glycolysis, also explored the underlying mechanism. Bioinformatics analysis and in vitro and in vivo research were used to reveal the role of SLC2A3 in macrophage infiltration and transition.

Results
Here, we show that SLC2A3 acts as a tumor promoter and accelerates aerobic glycolysis in GC cells. Mechanistically, the SLC2A3-STAT3-SLC2A3 feedback loop could promote phosphorylation of the STAT3 signaling pathway and downstream glycolytic targeting genes. Moreover, SLC2A3 potentially contributes to M2 subtype transition of macrophage infiltration in the GC microenvironment.

Conclusions
SLC2A3 could be used as a prognostic biomarker to determine prognosis and immune infiltration in GC and may provide an intervention strategy for GC therapy.
Aryl-hydrocarbon receptor binding and the incidence of type 2 diabetes: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Duncan Bruce B. , Castilhos Cristina D. , Bracco Paula A. , Schmidt Maria I. , Kang Sora , Im Suyeol , Lee Hong-Kyu , Vigo Álvaro , Pak Youngmi K. 
Published: October 2020

Abstract
Background
Persistent organic pollutants (POPs) may cause diabetes, in part through aryl hydrocarbon receptor (AhR) binding. Ensuing mitochondrial dysfunction is postulated to mediate this effect. We aim to investigate the association of POPs with incident diabetes indirectly by bio-assaying AhR ligand bioactivity and intracellular ATP level induced by participant serum samples.

Methods
In incident case-cohort analyses of one ELSA-Brasil center, 1605 eligible subjects without diabetes at baseline had incident diabetes ascertained by self-report, medication use, OGTT or HbA1c at follow-up 4 years later. We assayed AhR ligand bioactivity (AhRL) and intracellular ATP content, the latter reflecting the presence of mitochondria-inhibiting substances (MIS), following incubation of recombinant mouse Hepa1c1c7 cells with participant sera for 71 incident diabetes cases and 472 randomly selected controls.

Results
In multiply-adjusted proportional hazards regression analyses, those with above-median AhRL and below-median MIS-ATP had 69 and 226% greater risk of developing diabetes (HR = 1.69; 95%CI 1.01–2.83 and 3.26; 1.84–5.78), respectively. A strong interaction was seen between the two exposures (HRhigh AhRL/low MIS-ATP vs. low AhRL/high MIS-ATP = 8.15; 2.86–23.2).

Conclusion
The markedly increased incidence of diabetes seen in those with both higher AhR ligand bioactivity and increased mitochondrial inhibition supports the hypothesis that widespread POPs exposure contributes to the diabetes epidemic.
Health-related quality of life in breast cancer patients: review of reviews from 2008 to 2018
Authors: Mokhtari-Hessari Parisa , Montazeri Ali 
Published: October 2020

Abstract
Background
Breast cancer still is a topic. This overview of the literature aimed to update the current knowledge on quality of life in breast cancer patients.

Methods
A review of literature in MEDLINE, Cochrane Database of Systematic Reviews and Google Scholar were carried out to identify review papers on health-related quality of life in breast cancer during the 2008 to 2018. All publications were screened using the PRISMA guideline. The methodological quality of reviews was assessed using the AMSTAR. The findings were summarized and tabulated accordingly.

Results
Within over a decade, a total of 974 review papers were identified which according to the study selection criteria finally we have evaluated 82 reviews. Of these about 85% had a reasonable methodological quality. The findings were mainly summarized on several headings including instruments used to measure quality of life, treatment, supportive care, psychological distress, and symptoms. Questionnaires had a good performance to quantify quality of life in breast cancer patients. Most reviews were focused on the impact of treatment including endocrine therapy as well as integrating complementary and alternative medicine into the current practice. According to the reviews, yoga was the most recommended exercise to improve quality of life in breast cancer patients.

Conclusion
Overall, the findings from this overview indicated that quality of life in breast cancer patients enhanced during the last decade. Several simple but effective interventions such as physical activity and psychosocial interventions proved to be effective in improving quality of life in this population. However, management of symptoms such as pain, and lymphedema, issues related to worry, sexual function especially for young patients, and the future outlooks all are among topics that deserve further consideration. Also, this overview indicated that methodological issues in measuring quality of life in breast cancer patients improved greatly, but still there is a long way to go to understand what really matter to patients.
Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study
Authors: Giloteaux Ludovic , O’Neal Adam , Castro-Marrero Jesús , Levine Susan M. , Hanson Maureen R. 
Published: October 2020

AbstractBackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls.MethodsWe included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed.ResultsME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association.ConclusionsElevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.
The effect of breastfeeding education with grandmothers’ attendance on breastfeeding self-efficacy and infant feeding pattern in Iranian primiparous women: a quasi-experimental pilot study
Authors: Gharaei Tayebeh , Amiri-Farahani Leila , Haghani Shima , Hasanpoor-Azghady Syedeh Batool 
Published: October 2020

Abstract
Background
One of the most important factors that affects breastfeeding self-efficacy and exclusivity is breastfeeding support provided by the family. The aim of this study was to determine the effect of breastfeeding education sessions for primiparous women, with and without the attendance of maternal grandmothers, on breastfeeding self-efficacy and infant feeding patterns.

Methods
This quasi-experimental study was conducted on 64 primiparous women who referred to the Antenatal Clinic of Amiralmomenin Hospital, Tehran, Iran from June to December, 2018. Eligible pregnant women were allocated into two groups; either with and without grandmothers in attendance. Group assignments were determined according to the week the women had prenatal care at the hospital. All eligible women seen in the clinic during 1 week were assigned to one group and women who presented in the alternating week were assigned to the other group. In the education group with grandmothers in attendance, each woman participated in two prenatal education programs with her mother and one postpartum program approximately 3 h before discharge. In the other group, participating mothers attended breastfeeding education sessions without the grandmother’s attendance. The participating mothers answered questions from the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) at the time of the hospital discharge, and 4 and 8 weeks after delivery. Questions about the infants’ feeding patterns were asked by telephone contact with the participating mothers from both groups at the same time periods.

Results
The mean BFSE scores were signficantly different between the groups with grandmothers and without grandmothers at the time of the hospital discharge (60.15 ± 4.47 vs. 56.84 ± 6.22, independent t-test; p = 0.017), and at 4 weeks (61.71 ± 2.66 vs. 56.62 ± 9.12, p = 0.004) and 8 weeks after delivery (63.68 ± 2.14 vs. 60.03 ± 6.32, p = 0.003). No significant difference existed in infant feeding patterns between the groups at the same time periods.

Conclusions
This study suggests that breastfeeding education with grandmothers’ attendance is effective in improving the mothers’ breastfeeding self-efficacy. A family-centered program should be considered in beastfeeding education for increasing of exclusive breastfeeding.