bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1
Authors: Zhao Fei , Ke Jinjing , Pan Wensheng , Pan Hanghai , Shen Miao 
Published: January 2022

Abstract
Background
The increasing incidence of non-alcoholic fatty liver disease (NAFLD) has been reported worldwide, which urges understanding of its pathogenesis and development of more effective therapeutical methods for this chronic disease. In this study, we aimed to investigate the effects of a LIM homeodomain transcription factor, islet1 (ISL1) on NAFLD.

Methods
Male C57BL/6J mice were fed with a diet high in fat content to produce NAFLD models. These models were then treated with overexpressed ISL1 (oe-ISL1), oe-Lysine-specific demethylase 6B (KDM6B), oe-SNAI1, or short hairpin RNA against SNAI1. We assessed triglyceride and cholesterol contents in the plasma and liver tissues and determined the expressions of ISL1, KDM6B and SNAI1 in liver tissues. Moreover, the in vitro model of lipid accumulation was constructed using fatty acids to explore the in vitro effect of ISL1/KDM6B/SNAI1 in NAFLD.

Results
The results showed that the expressions of ISL1, KDM6B, and SNAI1 where decreased, but contents of triglyceride and cholesterol increased in mice exposed to high-fat diet. ISL1 inhibited lipogenesis and promoted lipolysis and exhibited a synergizing effect with KDM6B to upregulate the expression of SNAI1. Moreover, both KDM6B and SNAI1 could inhibit lipogenesis and induce lipolysis. Importantly, the therapeutic effects of ISL1 on in vitro model of lipid accumulations was also confirmed through the modulation of KDM6B and SNAI1.

Conclusions
Taken together, these findings highlighted that ISL1 effectively ameliorated NAFLD by inducing the expressions of KDM6B and SNAI1, which might be a promising drug for the treatment of NAFLD.
Mortality risks of body mass index and energy intake trajectories in institutionalized elderly people: a retrospective cohort study
Authors: Kawakami Yoshiaki , Hamano Jun 
Published: January 2022

Abstract
Background
Many factors can identify the mortality risks of institutionalized elderly people; among all such factors, body mass index (BMI) and energy intake (EI) can be employed as independent predictors. The objective of this study was to elucidate about the mortality risks and the trajectory of two parameters obtained from continuously monitored data.

Methods
This retrospective cohort study targeted 218 elderly people who were admitted to a nursing home for at least 6 months between 2007 and 2020 and passed away at the nursing home. BMI and EI (kcal) per body weight (BW) were continuously measured until death.

Results
BMI continued to decrease for 5 years until death. The rate of change of BMI significantly increased for 3 years before death (P = 0.004). In contrast, the rate of change of EI per BW significantly increased after 1 year before death (P < 0.001); in addition, 2 months before death, this rate of change significantly exceeded that of BMI (P = 0.007). In the four risk groups that were examined, a BMI of <18.0 + EI per BW of <29.2 and a BMI of <17.3 + EI per BW of <28.3 were significantly correlated with a high risk of death (log-rank test: P < 0.001, P = 0.002, respectively). There was no significant difference in the hazard ratio based on the age at the time of admission; however, when EI per BW was <23.8, the risk of death was significantly higher [hazard ratio = 4.36; 95% confidence interval: 2.31–8.24].

Conclusions
Elderly people in the current study presented a tendency toward decreasing BMI starting 60 months prior to death even if EI per BW remained constant. In the 1 year before death, EI per BW rapidly decreased. When the rate of change of EI per BW exceeded the rate of decrease of BMI, it was considered to be the point of no return when death was imminent. Our study showed that identifying mortality risks from the relationship between the trajectories of the two parameters that were continuously measured for several months to years is possible.
Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials
Authors: Vegivinti Charan Thej Reddy , Evanson Kirk W. , Lyons Hannah , Akosman Izzet , Barrett Averi , Hardy Nicole , Kane Bernadette , Keesari Praneeth Reddy , Pulakurthi Yashwitha Sai , Sheffels Erin , Balasubramanian Prasanth , Chibbar Richa , Chittajallu Spandana , Cowie Kathryn , Karon J. , Siegel Lauren , Tarchand Ranita , Zinn Caleb , Gupta Nitin , Kallmes Kevin M. , Saravu Kavitha , Touchette Jillienne 
Published: January 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment.

Methods
A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics.

Results
Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials.

Conclusions
Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.
Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study
Authors: Song Xinli , Li Qiongxuan , Diao Jingyi , Li Jinqi , Li Yihuan , Zhang Senmao , Zhao Lijuan , Chen Letao , Wei Jianhui , Shu Jing , Liu Yiping , Sun Mengting , Huang Peng , Wang Tingting , Qin Jiabi 
Published: January 2022

Abstract
Background
MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.

Methods
A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association.

Results
Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13–2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57–3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01–2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38–4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01–2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02–2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.

Conclusions
Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

Trial registration
Registration number: ChiCTR1800016635.
Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1
Authors: Lin Lele , Li Hongbo , Shi Dike , Liu Zhiqiang , Wei Yunhai , Wang Wei , Wu Dan , Li Baozhong , Guo Qingqu 
Published: January 2022

Abstract
Background
Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of C12orf48 in gastric cancer are largely unknown.

Methods
We used bioinformatics approaches and tissue microarray immunohistochemistry to analyze the expression profile of C12orf48 in gastric cancer tissues. Plasmid-mediated over-expression or knockdown were performed. CCK-8 assays and flow cytometry were employed to evaluate cellular proliferation and apoptosis respectively. Transwell assays were used to assess migrative and invasive abilities. The roles of C12orf48 were also evaluated in a xenograft tumor model.

Results
We found that C12orf48 was over-expressed in gastric cancer tissue, which associated with advanced stage and poor prognosis. In vitro and in vivo experiments showed depletion of C12orf48 attenuated cancer growth, while facilitated apoptosis. Further, the expression of Poly r(C)-Binding Protein (PCBP) 1 was found negatively regulated by C12orf48. Intended up-regulation of PCBP1 prevented C12orf48-mediated proliferation and rescued cells from apoptosis. Besides, C12orf48 promoted cellular migration and invasion, with E-cadherin down-regulated while vimentin and N-cadherin up-regulated, which was reversed by up-regulated PCBP1.

Conclusions
Our findings indicate that depletion of C12orf48 inhibited gastric cancer growth and metastasis via up-regulating PCBP1. Targeting C12orf48-PCBP1 axis may be a potential therapeutic strategy.
Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes
Authors: Shi Cong , Gong Shengping , Wu An , Yang Shujun , Zou Duobing , Zhang Yi , Wu Ningning , Ma Chao , Shi Songqiu , Chen Ying , Wu Ying , Zheng Xiaojiao , Huang Zhenya , Ding Jianghua , Ouyang Guifang , Mu Qitian 
Published: January 2022

Abstract
Background
Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients.

Methods
We retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models.

Results
MDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034).

Conclusions
Decreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.
Promotion of HepG2 cell apoptosis by Sedum emarginatum Migo and the mechanism of action
Authors: Qiu Qin , Jiang Lujuan , Zhen Hanshen , Huang Fengyin , Zhen Dandan , Ye Meifang , Meng Xueyan , Liu Yuanyuan , Qin Xijun 
Published: January 2022

Abstract
Background
Sedum emarginatum Migo(S. emarginatum) has anti-tumor and anti-oxidant effects. This study aimed to screen the extractions of S. emarginatum against liver cancer in vitro and explore its anti-liver cancer mechanism.

Methods
The CCK-8(Cell Counting Kit-8) method was used to detect the inhibitory effect of different extracts of S. emarginatum on the proliferation of liver cancer HepG2 cells. The morphological changes of the cells after administration were observed with microscopy, cell apoptosis was detected by flow cytometry, and the expression of Bax, Bcl-2 and Caspase-3 mRNA in the cells were detected by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) to explore the mechanism of action.

Results
CCK-8 method test results showed that among the different extracts of S. emarginatum, the ethyl acetate extract(1000 μg/ml, 2000 μg/ml, 2500 μg/ml, 3000 μg/ml) and n-butanol extract(1000 μg/ml, 2000 μg/ml, 2500 μg/ml, 3000 μg/ml) have the strongest inhibitory effect on the proliferation of HepG2 cells. In these 4 concentrations, the inhibitory effect increased as the concentration increased. The IC50 of the ethyl acetate extract on HepG2 cells was less than that of the n-butanol extract, so the ethyl acetate extract has a better proliferation inhibitory effect on HepG2 cells than the n-butanol extract, followed by the 70% ethanol extract(3000 μg/ml) and the water extract(3000 μg/ml), petroleum ether extract was the weakest. The results of microscopy showed that ethyl acetate extract caused hepatocarcinoma HepG2 cell morphology changed, cell density decreased, and suspension cells increased. Moreover, the results of flow cytometry showed that the ethyl acetate extract of S. emarginatum could induce HepG2 cell apoptosis at the concentrations of 2500μg/ml and 3000μg/ml. RT-PCR results showed that the expression of Bax mRNA was up-regulate by the middle(2500 μg/ml) and high(3000 μg/ml) dose groups of ethyl acetate extract. The expression of Caspase-3 mRNA was up-regulated by the low(2000 μg/ml), medium(2500 μg/ml) and high(3000 μg/ml) dose groups of ethyl acetate extract. The expression of Bcl-2 mRNA was down-regulated by the high(3000 μg/ml) dose group of ethyl acetate extract.

Conclusion
The ethyl acetate extract of S. emarginatum has the best effect on human liver cancer HepG2 cells. Its anti-hepatocellular mechanism may be related to affect the expression of apoptosis genes (Bax, Bcl-2 and Caspase-3mRNA) and promote the apoptosis of liver cancer cells. It provided a reference for the research and development of drugs for the treatment of liver cancer.
Investigating vaccine-induced immunity and its effect in mitigating SARS-CoV-2 epidemics in China
Authors: Liu Hengcong , Zhang Juanjuan , Cai Jun , Deng Xiaowei , Peng Cheng , Chen Xinghui , Yang Juan , Wu Qianhui , Chen Xinhua , Chen Zhiyuan , Zheng Wen , Viboud Cécile , Zhang Wenhong , Ajelli Marco , Yu Hongjie 
Published: January 2022

Abstract
Background
To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs.

Methods
We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided.

Results
We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50–62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021.

Conclusions
Efforts should be taken to increase population’s confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.
Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel
Authors: Gurioli Giorgia , Conteduca Vincenza , Brighi Nicole , Scarpi Emanuela , Basso Umberto , Fornarini Giuseppe , Mosca Alessandra , Nicodemo Maurizio , Banna Giuseppe Luigi , Lolli Cristian , Schepisi Giuseppe , Ravaglia Giorgia , Bondi Isabella , Ulivi Paola , De Giorgi Ugo 
Published: January 2022

Abstract
Background
Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor (AR) copy number (CN).

Methods
Patients receiving cabazitaxel 20 or 25 mg/sqm for mCRPC were enrolled. Digital PCR was performed to assess plasma AR CN status. CTC enrichment was assessed using the AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes. Data are expressed as hazard ratio (HR) or odds ratio (OR) and 95% CI.

Results
Seventy-four patients were fully evaluable. CTC expression of AR-V7 (HR=2.52, 1.24–5.12, p=0.011), AKR1C3 (HR=2.01, 1.06–3.81, p=0.031), AR (HR=2.70, 1.46–5.01, p=0.002), EPCAM (HR=3.75, 2.10–6.71, p< 0.0001), PSMA (HR=2.09, 1.19–3.66, p=0.01), MDK (HR=3.35, 1.83–6.13, p< 0.0001), and HPRT1 (HR=2.46, 1.44–4.18, p=0.0009) was significantly associated with OS. ALDH1 (OR=5.50, 0.97–31.22, p=0.05), AR (OR=8.71, 2.32–32.25, p=0.001), EPCAM (OR=7.26, 1.47–35.73, p=0.015), PSMA (OR=3.86, 1.10–13.50, p=0.035), MDK (OR=6.84, 1.87–24.98, p=0.004), and HPRT1 (OR=7.41, 1.82–30.19, p=0.005) expression was associated with early PD. AR CN status was significantly correlated with AR-V7 (p=0.05), EPCAM (p=0.02), and MDK (p=0.002) expression. In multivariable model, EPCAM and HPRT1 CTC expression, plasma AR CN gain, ECOG PS=2, and liver metastases and PSA were independently associated with poorer OS. In patients treated with cabazitaxel 20 mg/sqm, median OS was shorter in AR-V7 positive than negative patients (6.6 versus 14 months, HR=3.46, 1.47–8.17], p=0.004).

Conclusions
Baseline CTC biomarkers may be prognosticators for cabazitaxel-treated mCRPC patients. Cabazitaxel at lower (20 mg/sqm) dose was associated with poorer outcomes in AR-V7 positive patients compared to AR-V7 negative patients in a post hoc subgroup analysis.

Trial registration
Clinicaltrials.govNCT03381326. Retrospectively registered on 18 December 2017.
CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway
Authors: Wang Anqi , Yang Wen , Li Yue , Zhang Yang , Zhou Jieqi , Zhang Ruochen , Zhang Weijie , Zhu Jianjie , Zeng Yuanyuan , Liu Zeyi , Huang Jian-an 
Published: January 2022

Abstract
Background
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most lethal tumour worldwide. Copine 1 (CPNE1) was identified as a novel oncogene in NSCLC in our previous study. However, its specific function and relative mechanisms remain poorly understood.

Methods
The biological role of CPNE1 and RACK1 in NSCLC was investigated using gene expression knockdown and overexpression, cell proliferation assays, clonogenic assays, and Transwell assays. The expression levels of CPNE1, RACK1 and other proteins were determined by western blot analysis. The relationship between CPNE1 and RACK1 was predicted and investigated by mass spectrometry analysis, immunofluorescence staining, and coimmunoprecipitation. NSCLC cells were treated with a combination of a MET inhibitor and gefitinib in vitro and in vivo.

Results
We found that CPNE1 facilitates tumorigenesis in NSCLC by interacting with RACK1, which further induces activation of MET signaling. CPNE1 overexpression promoted cell proliferation, migration, invasion and MET signaling in NSCLC cells, whereas CPNE1 knockdown produced the opposite effects. In addition, the suppression of the enhancing effect of CPNE1 overexpression on tumorigenesis and MET signaling by knockdown of RACK1 was verified. Moreover, compared to single-agent treatment, dual blockade of MET and EGFR resulted in enhanced reductions in the tumour volume and downstream signaling in vivo.

Conclusions
Our findings show that CPNE1 promotes tumorigenesis by interacting with RACK1 and activating MET signaling. The combination of a MET inhibitor with an EGFR-TKI attenuated tumour growth more significantly than either single-drug treatment. These findings may provide new insights into the biological function of CPNE1 and the development of novel therapeutic strategies for NSCLC.
Application of community dialogue approach to prevent adolescent pregnancy, early marriage and school dropout in Zambia: a case study
Authors: Zulu Ireen Zamanga , Zulu Joseph Mumba , Svanemyr Joar , Michelo Charles , Mutale Wilbroad , Sandøy Ingvild Fossgard 
Published: January 2022

Abstract
Background
Adolescent pregnancy carries both health and economic risks for the pregnant girl and resulting baby, and it is common in Zambia. Providing alternative methods of preventing early pregnancy than abstinence is regarded as culturally and religiously unacceptable in most parts of the country. The community dialogue approach is being tested to address norms and beliefs around early pregnancy, marriage and school dropout, and is based on Paulo Freire’s transformative communication approach. The objective of this paper was to understand parents’ perspectives on the application of the community dialogue approach in addressing adolescents’ early pregnancy and school dropout in a cluster randomized controlled trial in rural Zambia.

Methods/design
This was a case study design. We nested the study in the community dialogue intervention arm of the Research Initiative to Support the Empowerment of Girls trial in Zambia. Dialogue meetings were held and economic support was provided for a period of 27 months from September 2016 until November 2018. We held focus group discussions in November 2018 with guardians/parents in six schools in Chibombo District of Central Province. All the discussions were audio recorded and transcribed verbatim. Thematic analysis was used to analyze the data.

Results
The guardians/parents perceived the community dialogue to be a relevant approach for addressing social and cultural norms regarding early pregnancy, marriage and school dropout. It was embraced for its value in initiating individual and collective change. The facilitators’ interactive approach and dialogue in the community meetings coupled with the use of films and role plays with the parents, lead to active participation and open discussions about sexual and reproductive health (SRH) topics during the community dialogue meetings. Group interactions and sharing of experiences helped parents clarify their SRH values and subsequently made them feel able to communicate about SRH issues with their children. However, cultural and religious beliefs among the parents regarding some topics, like the use of condoms and contraceptives, complicated the delivery of reproductive health messages from the parents to their children.

Conclusion
The study indicated that the community dialogue was appreciated by the parents and helped in addressing cultural barriers to discussing SRH issues between generations.