bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative contributions of statin intensity, achieved low-density lipoprotein cholesterol level, and statin therapy duration to cardiovascular risk reduction in patients with type 2 diabetes: population based cohort study
Authors: Kim Ji Yoon , Choi Jimi , Kim Sin Gon , Kim Nam Hoon 
Published: February 2022

Abstract
Background
Current guidelines recommend life-long use of statin for patients with type 2 diabetes (T2D), however, a number of patients discontinue statin therapy in clinical practice. We aimed to estimate the optimal statin therapy including statin therapy duration, statin intensity, and low-density lipoprotein cholesterol (LDL-C) level among patients with T2D in a real-world setting.

Methods
From Korean National Health Insurance Service Cohort (2007–2015), 8937 patients with T2D (≥ 40 years of age) who received statin therapy for at least 90 days were included. Risk of major adverse cardiovascular event (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death was estimated according to statin intensity, achieved serum LDL-C level, and statin therapy duration, respectively. The relative contributions of these factors to MACE risk were quantified by calculating the proportion of log-likelihood explained by each factor.

Results
The hazard ratio (HR) of MACE was lower in patients receiving moderate- or high-intensity statins than in those receiving low-intensity statins (HR, 0.72; p = 0.027). Among patients who received moderate- or high-intensity statins, lower achieved LDL-C level was associated with lower cardiovascular risk. Notably, the longer the patients received statins, the lower was the risk of MACE; the HR of MACE was significantly reduced after at least 18 months (adjusted HR, 0.70; p = 0.009) as a reference to 3–6 months of therapy. The proportion of explainable log-likelihood for MACE was greatest for statin duration (2.55), followed by achieved LDL-C level (2.18), and statin intensity (0.95).

Conclusions
Statin therapy duration is as important as or more crucial than statin intensity or achieved LDL-C level for the reduction of cardiovascular risk in T2D patients. The concept of “longer is better” regarding statin therapy should be considered in clinical practice.
Metabolic engineering of Escherichia coli for efficient biosynthesis of butyl acetate
Authors: Ku Jason T. , Chen Arvin Y. , Lan Ethan I. 
Published: February 2022

Abstract
Background
Butyl acetate is a versatile compound that is widely used in the chemical and food industry. The conventional butyl acetate synthesis via Fischer esterification of butanol and acetic acid using catalytic strong acids under high temperature is not environmentally benign. Alternative lipase-catalyzed ester formation requires a significant amount of organic solvent which also presents another environmental challenge. Therefore, a microbial cell factory capable of producing butyl acetate through fermentation of renewable resources would provide a greener approach to butyl acetate production.

Result
Here, we developed a metabolically engineered strain of Escherichia coli that efficiently converts glucose to butyl acetate. A modified Clostridium CoA-dependent butanol production pathway was used to synthesize butanol which was then condensed with acetyl-CoA through an alcohol acetyltransferase. Optimization of alcohol acetyltransferase expression and redox balance with auto-inducible fermentative controlled gene expression led to an effective titer of 22.8 ± 1.8 g/L butyl acetate produced in a bench-top bioreactor.

Conclusion
Building on the well-developed Clostridium CoA-dependent butanol biosynthetic pathway, expression of an alcohol acetyltransferase converts the butanol produced into butyl acetate. The results from this study provided a strain of E. coli capable of directly producing butyl acetate from renewable resources at ambient conditions.
HPV16 E6 gene polymorphisms and the functions of the mutation site in cervical cancer among Uygur ethnic and Han nationality women in Xinjiang, China
Authors: Xin Huizhen , Pan Zhenzhen , Zhe Xiangyi , Zhang Chunhe , Li Hongtao , Zheng Weinan , Long Haichen , Shao Renfu , Li Dongmei , Pan Zemin 
Published: February 2022

Abstract
Background
To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang, China; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer.

Methods
The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-T295/T350, G295/G350, and T295/G350 GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments.

Results
The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. T295/G350-E6 was significantly stronger than G295/G350 and T295/T350, G295/G350 was significantly stronger than T295/T350 (P < 0.05). The T295/G350 had the strongest effect on C33A cells and G295/G350 was significantly stronger than T295/T350 (P < 0.05).

Conclusions
The positive HPV infection rates differed between the Uygur and Han in Xinjiang, China, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the T295/G350 mutation site promoted the proliferation, migration, and invasion of C33A cells to a greater extent than G295/G350; however, G295/G350 had a stronger effect than T295/T350.
A novel qualitative signature based on lncRNA pairs for prognosis prediction in hepatocellular carcinoma
Authors: Bu Xiaoyun , Ma Luyao , Liu Shuang , Wen Dongsheng , Kan Anna , Xu Yujie , Lin Xuanjia , Shi Ming 
Published: February 2022

AbstractBackgroundPrognostic assessment is imperative for clinical management of patients with hepatocellular carcinoma (HCC). Most reported prognostic signatures are based on risk scores summarized from quantitative expression level of candidate genes, which are vulnerable against experimental batch effects and impractical for clinical application. We aimed to develop a robust qualitative signature to assess individual survival risk for HCC patients.MethodsLong non-coding RNA (lncRNA) pairs correlated with overall survival (OS) were identified and an optimal combination of lncRNA pairs based on the majority voting rule was selected as a classification signature to predict the overall survival risk in the cancer genome atlas (TCGA). Then, the signature was further validated in two external datasets. Besides, biomolecular characteristics, immune infiltration status, and chemotherapeutics efficacy of different risk groups were further compared. Finally, we performed key lncRNA screening and validated it in vitro.ResultsA signature consisting of 50 lncRNA pairs (50-LPS) was identified in TCGA and successfully validated in external datasets. Patients in the high-risk group, when at least 25 of the 50-LPS voted for high risk, had significantly worse OS than the low-risk group. Multivariate Cox, receiver operating characteristic (ROC) curve and decision curve analyses (DCA) demonstrated that the 50-LPS was an independent prognostic factor and more powerful than other available clinical factors in OS prediction. Comparison analyses indicated that different risk groups had distinct biomolecular characteristics, immune infiltration status, and chemotherapeutics efficacy. TDRKH-AS1 was confirmed as a key lncRNA and associated with cell growth of HCC.ConclusionsThe 50-LPS could not only predict the prognosis of HCC patients robustly and individually, but also provide theoretical basis for therapy. Besides, TDRKH-AS1 was identified as a key lncRNA in the proliferation of HCC. The 50-LPS might guide personalized therapy for HCC patients in clinical practice.
Identification and validation a costimulatory molecule gene signature to predict the prognosis and immunotherapy response for hepatocellular carcinoma
Authors: Hu Yinan , Liu Jingyi , Yu Jiahao , Yang Fangfang , Zhang Miao , Liu Yansheng , Ma Shuoyi , Zhou Xia , Wang Jingbo , Han Ying 
Published: February 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Costimulatory molecules have been proven to be the foundation of immunotherapy. However, the potential roles of costimulatory molecule genes (CMGs) in HCC remain unclear. Our study is aimed to develop a costimulatory molecule-related gene signature that could evaluate the prognosis of HCC patients.

Methods
Based on The Cancer Gene Atlas (TCGA) database, univariate Cox regression analysis was applied in CMGs to identify prognosis-related CMGs. Consensus clustering analysis was performed to stratify HCC patients into different subtypes and compared them in OS. Subsequently, the LASSO Cox regression analysis was performed to construct the CMGs-related prognostic signature and Kaplan–Meier survival curves as well as ROC curve were used to validate the predictive capability. Then we explored the correlations of the risk signature with tumor-infiltrating immune cells, tumor mutation burden (TMB) and response to immunotherapy. The expression levels of prognosis-related CMGs were validated based on qRT-PCR and Human Protein Atlas (HPA) databases.

Results
All HCC patients were classified into two clusters based on 11 CMGs with prognosis values and cluster 2 correlated with a poorer prognosis. Next, a prognostic signature of six CMGs was constructed, which was an independent risk factor for HCC patients. Patients with low-risk score were associated with better prognosis. The correlation analysis showed that the risk signature could predict the infiltration of immune cells and immune status of the immune microenvironment in HCC. The qRT-PCR and immunohistochemical results indicated six CMGs with differential expression in HCC tissues and normal tissues.

Conclusion
In conclusion, our CMGs-related risk signature could be used as a prediction tool in survival assessment and immunotherapy for HCC patients.
Thermo/pH dual-responsive micelles based on the host–guest interaction between benzimidazole-terminated graft copolymer and β-cyclodextrin-functionalized star block copolymer for smart drug delivery
Authors: Adeli Floria , Abbasi Farhang , Babazadeh Mirzaagha , Davaran Soodabeh 
Published: February 2022

AbstractNovel temperature and pH dual-sensitive amphiphilic micelles were fabricated exploiting the host–guest interaction between benzimidazole-terminated PHEMA-g-(PCL-BM) and β-CD-star-PMAA-b-PNIPAM. The fabricated graft copolymer had a brush-like structure with star side chains. The micelles were utilized as dual-responsive nanocarriers and showed the LCST between 40 and 41 °C. The acidic pH promoted the dissociation of the PHEMA-g-(PCL-BM: β-CD-star-PMAA-b-PNIPAM) micelles. DOX.HCl was loaded into the core of the micelles during self-assembly in an aqueous solution with a high encapsulation efficacy (97.3%). The average size of the amphiphilic micelles was about 80 nm, suitable size for the enhanced permeability and retention effect in tumor vasculature. In an aqueous environment, these micelles exhibited very good self-assembly ability, low CMC value, rapid pH- and thermo-responsiveness, optimal drug loading capacity, and effective release of the drug. The biocompatibility was confirmed by the viability assessment of human breast cancer cell line (MCF-7) through methyl tetrazolium assay. DOX-loaded micelles displayed excellent anti-cancer activity performance in comparison with free DOX.
Graphical Abstract
Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy
Authors: Huang Xiuyu , Qiu Miaojuan , Wang Tianqi , Li Binbin , Zhang Shiqiang , Zhang Tianzhi , Liu Peng , Wang Qiang , Qian Zhi Rong , Zhu Chengming , Wu Meiying , Zhao Jing 
Published: February 2022

AbstractBackgroundOvarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect.Methods and resultsIn this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice.ConclusionIn summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.Graphical Abstract
The portrayal and perceptions of cesarean section in Mexican media Facebook pages: a mixed-methods study
Authors: Vazquez Corona Martha , Betrán Ana Pilar , Bohren Meghan A. 
Published: February 2022

Abstract
Background
Mexico has one of the highest rates of cesarean sections globally at over 45%. There is limited research about social factors influencing these rates. This study explores the portrayal and perceptions of cesarean section in Facebook media pages to better understand the socio-cultural context of childbirth in Mexico.

Methods
This is a mixed-methods social media analysis using two data sources. First, to study the portrayal of cesarean section, we identified ten Mexican media Facebook pages with the largest audiences (based on number of page “likes”). We searched these pages for articles containing the word “cesárea” (Spanish for cesarean section), and posts (articles) were eligible for inclusion if they contained the word “cesárea”. Second, to understand perceptions of cesarean section portrayal, we extracted comment threads of each Facebook post sharing the included articles. We performed a qualitative thematic analysis of articles and a quantitative content analysis of comments.

Results
We included 133 Facebook posts depicting 80 unique articles and identified three major themes: (1) information about cesarean section, (2) inequality and violence against women, (3) governance failures. Cesarean section was portrayed as a lifesaving procedure when medical necessary, and riskier than vaginal birth, with a longer recovery time, and possible negative health consequences. We extracted comments from 133 Facebook posts, and 6350 comments were included. We inductively developed 20 codes to then classify comments under six major categories: (1) violence and discrimination, (2) health and health services, (3) mode of birth choice, (4) disbelief at information about cesarean section, (5) abortion, and (6) discontent at the government.

Conclusions
We found that Facebook media did not promote cesarean section over vaginal birth, and risks and consequences were mostly represented reliably. Perceptions about the portrayal of cesarean section showed strong discontent and distrust against providers and the health system, as well as rejection of factual information about the consequences of cesarean section. We documented gross gender inequality and violence against women, highlighting the urgent need for human rights approaches to maternal health to address these inequalities and prevent harmful practices. Our study also contributes to the emerging field of social media analysis, and demonstrates clear areas where social media communication can be improved.
Woman and girl-centred care for those affected by female genital mutilation: a scoping review of provider tools and guidelines
Authors: Dawson Angela , Assifi Anisa , Turkmani Sabera 
Published: February 2022

AbstractBackgroundA woman and girl centred, rights-based approach to health care is critical to achieving sexual and reproductive health. However, women with female genital mutilation in high-income countries have been found to receive sub-optimal care. This study examined documents guiding clinicians in health and community service settings in English-speaking high-income countries to identify approaches to ensure quality women and girl-centred care for those with or at risk of female genital mutilation.MethodWe undertook a scoping review using the integrative model of patient-centredness to identify principles, enablers, and activities to facilitate woman and girl-centred care interactions. We developed an inclusion criterion to identify documents such as guidance statements and tools and technical guidelines, procedural documents and clinical practice guidelines. We searched the databases and websites of health professional associations, ministries of health, hospitals, national, state and local government and non-government organisations working in female genital mutilation in the United Kingdom, Ireland, Canada, The United States, New Zealand, and Australia. The Appraisal of Guidelines for Research and Evaluation tool was used to appraise screened documents.FindingsOne-hundred and twenty-four documents were included in this scoping review; 88 were developed in the United Kingdom, 20 in Australia, nine in the United States, three in Canada, two in New Zealand and two in Ireland. The focus of documents from the United Kingdom on multi-professional safeguarding (62), while those retrieved from Australia, Canada, Ireland, New Zealand and the US focused on clinical practice. Twelve percent of the included documents contained references to all principles of patient-centred care, and only one document spoke to all principles, enablers and activities.ConclusionThis study demonstrates the need to improve the female genital mutilation-related guidance provided to professionals to care for and protect women and girls. Professionals need to involve women and girls with or at risk of female genital mutilation in the co-design of guidelines and tools and evaluation of them and the co-production of health care.
CD161 expression defines new human γδ T cell subsets
Authors: Karunathilaka Amali , Halstrom Samuel , Price Patricia , Holt Michael , Lutzky Viviana P. , Doolan Denise L. , Kupz Andreas , Bell Scott C. , Thomson Rachel M. , Miles John J. , Ratnatunga Champa N. 
Published: February 2022

Abstractγδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi−parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1−subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease.
Redressing COVID-19 vaccine inequity amidst booster doses: charting a bold path for global health solidarity, together
Authors: Rackimuthu Sudhan , Narain Kapil , Lal Arush , Nawaz Faisal A. , Mohanan Parvathy , Essar Mohammad Yasir , Charles Ashworth Henry 
Published: February 2022

Abstract
Background
With large swathes of the world’s population—majority clustered in low- and middle-income countries—still yet to receive the minimum of two doses of the COVID-19 vaccine; The need to address the failures of international solidarity to equitably distribute COVID-19 vaccines is now more urgent than ever to help curb the pandemic and prevent future variants. However, many high-income countries have adopted a “me first” approach, proceeding to offer COVID-19 booster doses to their entire populations, including those at least risk of severe illness, whilst the rest of the world is left unvaccinated or partially vaccinated with one dose for even their most vulnerable communities.

Main body
COVID-19 vaccine inequity places the health of the global population at risk and exacerbates socio-economic repercussions, especially in low- and middle-income countries. Initiatives launched to combat vaccine inequity such as the Fair Allocation Framework for the COVID-19 Vaccines (COVAX) have been unsuccessful as several governments, primarily from high-income countries, have scaled down their contributions to the initiative. Furthermore, COVAX has not seriously engaged with the Access to COVID-19 Tools (ACT) Health Systems Connector, as was originally intended, leading to crucial health systems components critical to vaccine delivery to be overlooked. Several strategies can be employed to help achieve the desired global immunization goals, such as Intellectual Property waivers, increased donations, and activation of new COVID-19 vaccine manufacturing hubs. In addition, continued advocacy for vaccine equity by all involved and affected stakeholders, as well as critical amendments to existing or upcoming legislation and funding mechanisms will help address the shortcomings of current inequitable vaccine distribution.

Conclusions
Global solidarity and collective action through pandemic governance mechanisms are urgently needed to ensure vaccine equity. These interventions are vital to rapidly mitigate ongoing health and humanitarian crises and ultimately curb the pandemic, sooner rather than later.