bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model
Authors: Liu Xiang-Yu , Zhu Mao-Hua , Wang Xiao-Yu , Dong Xiao , Liu Hai-Jun , Li Rui-Yang , Jia Shi-Chong , Lu Qin , Zhao Mei , Sun Peng , Chen Hong-Zhuan , Fang Chao 
Published: January 2022

Abstract
Background
Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy.

Methods
NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated.

Results
Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice.

Conclusions
The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.

Graphical Abstract
How has the COVID-19 epidemic affected the risk behaviors of people who inject drugs in a city with high harm reduction service coverage in Vietnam? A qualitative investigation
Authors: Nguyen Trang Thu , Hoang Giang Thi , Nguyen Duc Quang , Nguyen Anh Huu , Luong Ngoc Anh , Laureillard Didier , Nagot Nicolas , Des Jarlais Don , Duong Huong Thi , Nham Thanh Thi Tuyet , Khuat Oanh Thi Hai , Pham Khue Minh , Le Mai Sao , Michel Laurent , Rapoud Delphine , Le Giang Minh 
Published: January 2022

Abstract
Introduction
The COVID-19 outbreak disproportionally affects vulnerable populations including people who inject drugs (PWID). Social distancing and stay-at-home orders might result in a lack of access to medical and social services, poorer mental health, and financial precariousness, and thus, increases in HIV and HCV risk behaviors. This article explores how the HIV/HCV risk behaviors of PWID in Haiphong, a city with high harm reduction service coverage in Vietnam, changed during the early phase of the COVID-19 pandemic, and what shaped such changes, using the risk environment framework.

Method
We conducted three focus group discussions with peer outreach workers in May 2020 at the very end of the first lockdown, and 30 in-depth interviews with PWID between September and October 2020, after the second wave of infection in Vietnam. Discussions and interviews centered on the impact of the COVID-19 pandemic on their lives, and how their drug use and sexual behaviors changed as a result of the pandemic.

Results
The national shutdown of nonessential businesses due to the COVID-19 epidemic caused substantial economic challenges to participants, who mostly were in a precarious financial situation before the start of the epidemic. Unsafe injection is no longer an issue among our sample of PWID in Haiphong thanks to a combination of different factors, including high awareness of injection-related HIV/HCV risk and the availability of methadone treatment. However, group methamphetamine use as a means to cope with the boredom and stress related to COVID-19 was common during the lockdown. Sharing of smoking equipment was a standard practice. Female sex workers, especially those who were active heroin users, suffered most from COVID-related financial pressure and may have engaged in unsafe sex.

Conclusion
While unsafe drug injection might no longer be an issue, group methamphetamine use and unsafe sex were the two most worrisome HIV/HCV risk behaviors of PWID in Haiphong during the social distancing and lockdown periods. These elevated risks could continue beyond the enforced lockdown periods, given PWID in general, and PWID who are also sex workers in particular, have been disproportionately affected during the global crisis.
Rural population’s preferences matter: a value set for the EQ-5D-3L health states for China’s rural population
Authors: Liu Gordon G. , Guan Haijing , Jin Xuejing , Zhang Han , Vortherms Samantha A. , Wu Hongyan 
Published: January 2022

Abstract
Purpose
To develop an EQ-5D-3L social value set based on Chinese rural population’s preferences using the time trade-off (TTO) method, and to compare the differences in preferences on health states between China urban and rural population.

Methods
Between Sep 2013 and Nov 2013, a total of 1201 participants were recruited from rural areas of five Chinese cities (Beijing, Chengdu, Guiyang, Nanjing, and Shenyang) using a quota sampling method. Each respondent valued 13 health states using the TTO, and a total of 97 EQ-5D-3L health states were directly valued for estimating the value set. Various models with different specifications were explored at both aggregate and individual levels. The final model was determined by a set of predefined selection criteria.

Findings
An ordinary least square model at the aggregate level included 10 dummy variables for specifying the level 2 and 3 for each dimension and an N3 term presenting any dimension on level 3 was selected as the final model. The final model provides a value set ranges from − 0.218 to 0.859. The predicted utility values were highly correlated with but consistently lower than that of the published Chinese EQ-5D-3L value set (for urban population).

Conclusion
The availability of the China rural value set provides a set of social preferences weights for researchers and policy decision-makers for use in China rural area.
Quality of life of women with breast cancer in a tertiary referral university hospital
Authors: Yusoff Jamilah , Ismail Aniza , Abd Manaf Mohd Rizal , Ismail Fuad , Abdullah Norlia , Muhammad Rohaizak , Abdullah Suhaimi Shahrun Niza , Mat Zin Reena Rahayu 
Published: January 2022

Abstract
Background
Quality of life (QoL) is one of the treatment outcome measures in patients with breast cancer. In this study, we measured the QoL of women with breast cancer at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and identified the associated factors.

Methodology
This cross-sectional study was conducted from October 2017 to December 2017 and involved female patients with breast cancer. The QoL scores and domains were determined using the EuroQol EQ-5D-5L, and were presented as the utility value and visual analog scores, respectively.

Results
We recruited a total of 173 women, aged 33–87 years. The median VA score was 80.00 (interquartile range [IQR] 70.00–90.00); the median utility value was 0.78 (interquartile range [IQR] 0.65–1.00. Women who did not take traditional medicine had a higher utility index score of 0.092 (95% CI 0.014–0.171), and women with household income of RM3000–5000 had a higher utility index score of 0.096 (95% CI 0.011–0.180).

Conclusion
Traditional medicine consumption and household income were significantly associated with lower QoL. The pain/discomfort domain was the worst affected QoL domain and was related to traditional medicine use and household income. Addressing pain management in patients with breast cancer and the other factors contributing to lower QoL may improve the QoL of breast cancer survivors in the future.
Online faculty development in low- and middle-income countries for health professions educators: a rapid realist review
Authors: Keiller Lianne , Nyoni Champion , van Wyk Chantel 
Published: January 2022

AbstractBackgroundHealth professions educators require support to develop teaching and learning, research, educational leadership, and administrative skills to strengthen their higher education role through faculty development initiatives. Where administration has pursued face-to-face and online faculty development initiatives, results have positively influenced health professions educators. There is limited evidence demonstrating how online faculty development works for health professions educators in low- and middle-income countries who engage in online health professions education (HPE) faculty development.MethodsA Conjecture Map for online HPE faculty development courses identified candidate theories for a rapid realist review. The Conjecture Map and candidate theories, Community of Inquiry and the Conversational Framework guided the development of search terms and analysis for this review. Three searches using EbscoHost databases yielded 1030 abstracts. A primary and secondary research team participated in a multi-reviewer blinded process in assessing abstracts, selecting full-text articles, and data extraction. The primary research team analysed eight articles for this rapid realist review to answer the research question: How do online HPE faculty development courses work, or not work, in low- and middle-income countries? Data were analysed and mapped to the initial Conjecture Map and the research question.ResultsThe research references US-based organisations forming partnerships with low- and middle-income countries, and who provide funding for online HPE faculty development initiatives. These initiatives design courses that facilitate learning through engagement from which participants report beneficial outcomes of professional and career development. The review does not clarify if the reported outcomes are generalisable for facilitators from low-and middle-income countries. The findings of this review demonstrate the role of a community of practice as the dominant mechanism through which the outcomes are achieved, based on a design that incorporates six triggering events. The design aligns the triggering events with the three categories of the Community of Inquiry—a theory for designing online learning environments.ConclusionHealth professions educators in low- and middle-income countries can develop professional and interpersonal skills through a well-designed, specifically constructed online community that prioritises active discussion.
Subtyping of sarcomas based on pathway enrichment scores in bulk and single cell transcriptomes
Authors: Li Shengwei , Liu Qian , Zhou Haiying , Lu Hui , Wang Xiaosheng 
Published: January 2022

AbstractBackgroundSarcomas are highly heterogeneous in molecular, pathologic, and clinical features. However, a classification of sarcomas by integrating different types of pathways remains mostly unexplored.MethodsWe performed hierarchical clustering analysis of sarcomas based on the enrichment scores of 14 pathways involved in immune, stromal, DNA damage repair (DDR), and oncogenic signatures in three bulk tumor transcriptome datasets.ResultsConsistently in the three datasets, sarcomas were classified into three subtypes: Immune Class (Imm-C), Stromal Class (Str-C), and DDR Class (DDR-C). Imm-C had the strongest anti-tumor immune signatures and the lowest intratumor heterogeneity (ITH); Str-C showed the strongest stromal signatures, the highest genomic stability and global methylation levels, and the lowest proliferation potential; DDR-C had the highest DDR activity, expression of the cell cycle pathway, tumor purity, stemness scores, proliferation potential, and ITH, the most frequentTP53mutations, and the worst survival. We further validated the stability and reliability of our classification method by analyzing a single cell RNA-Seq (scRNA-seq) dataset. Based on the expression levels of five genes in the pathways of T cell receptor signaling, cell cycle, mismatch repair, focal adhesion, and calcium signaling, we built a linear risk scoring model (ICMScore) for sarcomas. We demonstrated that ICMScore was an adverse prognostic factor for sarcomas and many other cancers.ConclusionsOur classification method provides novel insights into tumor biology and clinical implications for sarcomas.
The ILEI/LIFR complex induces EMT via the Akt and ERK pathways in renal interstitial fibrosis
Authors: Zhou Jieqing , Jiang Hong , Jiang Hongkun , Fan Yan , Zhang Jing , Ma Xiaoxue , Yang Xuewei , Sun Yu , Zhao Xing 
Published: January 2022

Abstract
Background
Chronic kidney disease (CKD) is characterized by high morbidity and mortality and is difficult to cure. Renal interstitial fibrosis (RIF) is a major determinant of, and commonly occurs within, CKD progression. Epithelial mesenchymal transition (EMT) has been identified as a crucial process in triggering renal interstitial fibrosis (RIF). Interleukin‐like EMT inducer (ILEI) is an important promotor of EMT; this study aims to elucidate the mechanisms involved.

Methods
Male C57BL6/J mouse were randomly divided into 6 groups: sham (n = 10), sham with negative control (NC) shRNA (sham + NC, n = 10), sham with ILEI shRNA (sham + shILEI, n = 10), unilateral ureteral obstruction (UUO, n = 10), UUO with NC (UUO + NC, n = 10) and UUO with ILEI shRNA (UUO + shILEI, n = 10). Hematoxylin and eosin (H&E), Masson, and immunohistochemical (IHC) staining and western blotting (WB) were performed on murine kidney tissue to identify the function and mechanism of ILEI in RIF. In vitro, ILEI was overexpressed to induce EMT in HK2 cells and analyzed via transwell, WB, real-time PCR, and co-immunoprecipitation. Finally, tissue from 12 pediatric CKD patients (seven with RIF and five without RIF) were studied with H&E, Masson, and IHC staining.

Results
Our in vitro model revealed that ILEI facilitates RIF in the UUO model via the Akt and ERK pathways. Further experiments in vivo and in vitro revealed that ILEI promotes renal tubular EMT by binding and activating leukemia inhibitory factor receptor (LIFR), in which phosphorylation of Akt and ERK is involved. We further find markedly increased expression levels of ILEI and LIFR in kidneys from pediatric CKD patients with RIF.

Conclusion
Our results indicate that ILEI may be a useful biomarker for renal fibrosis and a potential therapeutic target for modulating RIF.
Information-seeking behavior on sexually transmitted infections and its associated factors among university students in Ethiopia: a cross-sectional study
Authors: Shimie Aynadis Worku , Gashu Kassahun Dessie , Shiferaw Atsede Mazengia , Mengiste Shegaw Anagaw 
Published: January 2022

Abstract
Background
Sexually Transmitted Infections (STIs) are infections commonly spread through sexual contact and transmitted by bacteria, viruses, or parasites. In today’s world, STI-related information-seeking behavior is often vital for the advancement of knowledge, behavioral changes, health decisions, and the sharing of sexual health information among youths. However, paucity of evidence on information-seeking behavior among students in higher education institutions. This study aimed to assess STI-related information-seeking behavior and its associated factors among students at the University of Gondar.

Methods
An institution-based cross-sectional quantitative study was conducted among students at the University of Gondar from January 15 to February 15, 2021. A total of 832 participants were selected using a stratified two-stage sampling method. A structured self-administered questionnaire was used to collect the required data. STI information-seeking behavior questionnaire was adapted from health information national survey tool (HINTS). Descriptive statistics, bi-variable, and multivariable logistic regression analyses were applied using SPSS version 26.

Result
The proportion of STI related information-seeking among university students was 462 (55.5%) with 95% CI (52.3, 58.9). About 263 (56.9%) of students preferred internet as a primary source for STI related information. Year of study being 4th (AOR = 4.77, 95% CI = 2.75, 8.29) and 5th year (AOR = 5.45, 95% CI = 2.48, 12.01), field of study being health (AOR = 2.19, 95% CI = 1.16, 4.11), sexual experiences (AOR = 2.33, 95% CI = 1.56, 3.48), ever had STI symptoms (AOR = 4.19, 95% CI = 2.14, 8.18), perceived susceptibility (AOR = 5.05, 95% CI = 3.29, 7.75), and perceived severity (AOR = 2.16,95% CI = 1.45, 3.22) were significant factors for good STI information-seeking.

Conclusion
the proportion of STI information-seeking among university students was low. Students' STI information-seeking behavior could be improved by increasing digital literacy and enhancing computer and internet access across the campus.
Factors affecting optimal adherence to antiretroviral therapy and viral suppression amongst HIV-infected prisoners in South Ethiopia: a comparative cross-sectional study
Authors: Fuge Terefe Gone , Tsourtos George , Miller Emma R. 
Published: January 2022

Abstract
Background
Maintaining optimal adherence and viral suppression in people living with HIV (PLWH) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of treatment adherence and viral suppression in incarcerated populations in low-income countries is unknown. This study aimed to determine factors affecting optimal adherence to antiretroviral therapy and viral suppression amongst HIV-infected prisoners in South Ethiopia.

Methods
A comparative cross-sectional study was conducted between June 1, 2019 and May 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWH. Patient information including demographic, socio-economic, behavioral, and incarceration-related characteristics were collected using a structured questionnaire. Medication adherence was assessed according to self-report and pharmacy refill. Plasma viral load measurements undertaken within the study period were prospectively extracted to determine viral suppression. Univariate and multivariate logistic and fractional regression models were used to analyse data.

Results
Seventy-four inmates living with HIV (ILWH) and 296 non-incarcerated PLWH participated in the study. While ILWH had a significantly higher pharmacy refill adherence compared to non-incarcerated PLWH (89 vs 75%), they had a slightly lower dose adherence (81% vs 83%). The prevalence of viral non-suppression was also slightly higher in ILWH (6.0%; 95% confidence interval (CI): 1.7–14.6%) compared to non-incarcerated PLWH (4.5%; 95%CI: 2.4–7.5%). Overall, missing ART appointments, dissatisfaction with ART services, inability to comply with a specified medication schedule, and types of methods used to monitor the schedule (e.g., news time on radio/TV or other social cues) were significantly associated with non-adherence according to self-report. In ILWH specifically, accessing ART services from a hospital, inability to properly attend clinic appointments, depressive symptoms, and lack of social support predicted NA. Viral non-suppression was significantly higher in males, people of age 31to 35 years and in those who experienced social stigma, regardless of their incarceration status.

Conclusions
Sub-optimal dose adherence and viral suppression are generally higher in HIV-infected prisoners in South Ethiopia compared to their non-incarcerated counterparts. A multitude of factors were found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.
Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B
Authors: Laras Andreas , Papatheodoridi Margarita , Panopoulou Eleni , Papatheodoridis George V. , Hadziyannis Stephanos J. , Hadziyannis Emilia 
Published: January 2022

Abstract
Background
Serum hepatitis B virus (HBV) RNA is a surrogate biomarker for intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity and persistence. In this retrospective study, we investigated its presence, levels and composition in ab initio Hepatitis B e antigen (HBeAg) negative chronically infected patients and examined possible associations with disease activity and the outcome of nucleos(t)ide analogue (NA) discontinuation.

Methods
We developed a sensitive real time polymerase chain reaction (RT-PCR) for the specific detection of HBV pregenomic RNA (pgRNA) and precore (preC) mRNA and analyzed 220 serum specimens, 160 under NA treatment, from 116 Greek patients initially negative for HBeAg.

Results
HBV pgRNA was detected in 31% and preC mRNA in 15% of samples, at lower levels representing a small fraction (3.4%) of total core promoter produced transcripts. In the absence of NAs, pgRNA was detected in 57% of samples with median value of 5.19 (2.61–8.35) log10 cp/mL, at lower levels than HBV DNA and correlated significantly with ALT (r = 0.764) and serum HBV DNA (r = 0.906). A wide range of HBV DNA/pgRNA ratio was observed with significant inter- and intra-patient variation. During NA treatment, pgRNA displayed low detectability (22%) and variable levels, median 3.97 (2.30– 8.13) log10 cp/mL, as well as, a significant inverse correlation with the duration of treatment (r = − 0.346, p < 0.01). In 74 events of NA discontinuation, end-of-treatment pgRNA-positive compared to pgRNA-negative cases, experienced more frequently virological (p = 0.016) and clinical (p = 0.011) relapse.

Conclusions
In genotype D ab initio HBeAg negative patients, serum HBV RNA is primarily composed of pgRNA plus a minor fraction of preC mRNA transcripts. Serum pgRNA is associated with disease activity, suggesting lysis of infected hepatocytes as a possible source of serum HBV RNA in untreated patients and in the early phase of NA treatment. During long term NA treatment, detectable serum pgRNA predicts viral rebound and clinical relapse following treatment discontinuation and may thus serve as a marker for the decision of cessation of therapy.