bluuebunny/crossref_metadata_2025 huggingface dataset:
Fostering university students’ learning performance using the one-take video approach
Authors: Börger Julian , Spilles Markus , Krull Johanna , Hagen Tobias , Hennemann Thomas
Published: January 2022

Various studies have shown that video-based learning by explaining to a fictitious audience can be an effective learning strategy for promoting multiple knowledge domains such as memory, comprehension and knowledge transfer. However, field studies testing the effectiveness of this learning strategy in an applied setting are rare. The present study examines the effectiveness of the one-take video (OTV) approach on undergraduate students’ learning performance. The OTV method involves users recording short oral presentations without any editing and with the support of handwritten visualisations (video-based learning by explaining). To test the learning outcomes, 218 undergraduate teaching students for special educational needs were randomly assigned to two test groups (OTV and explaining in writing). After that, they completed three study tasks throughout the semester, each followed by immediate and delayed knowledge tests. The results for the OTV group show that students achieved significantly better results in the immediate memory test the more handwritten visualisations they used, but not the more often they repeated the video recordings. Analyses of variance revealed that the OTV group outperformed the writing group in terms of memory performance in the immediate test but not in the delayed posttest. The OTV group also significantly outperformed the writing group in both posttests in the transfer domain. No significant differences were found in the comprehension test scores.
The Prevalence and Death Risk of Male Breast Cancer: A Study Based on the Surveillance, Epidemiology, and End Results Database
Authors: Cui Xiaofei
Published: January 2022

This study was to investigate the prevalence and death risk of male breast cancer (MBC) patients. The prevalence trend was based on the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. A competitive risk analysis was performed to analyze the death risk of MBC patients. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated. The results indicated that the prevalence of MBC after the standardization of the total population increased in 1975–2017 and its annual percentage change (APC) was 0.536% (95% CI = [0.362%, 0.713%]). The prevalence of MBC was rapidly increased in patients aged ≥70 years (APC = 0.780%; 95% CI = [0.491%, 1.076%]) and Grade Ⅱ tumors (APC = 1.462%; 95% CI = [1.260%, 1.686%]). The 1-, 3-, and 5-year cumulative mortality of MBC patients who died of MBC was 2.23% (95% CI = [1.61%, 2.85%]), 7.56% (95% CI = [6.33%, 8.78%]), and 13.10% (95% CI = [11.10%, 11.32%]), respectively. Competitive risk analysis demonstrated that Blacks (HR = 1.76; 95% CI = [1.12, 2.77]), Grade 3 (HR = 2.56; 95% CI = [1.03, 6.35]), AJCC (American Joint Committee on Cancer) Stage Ⅲ (HR = 3.04; 95% CI = [1.76, 5.26]), and AJCC Stage Ⅳ (HR = 7.27; 95% CI = [1.36, 38.83]) were associated with an increased MBC-specific death risk, whereas married status (HR = 0.40; 95% CI = [0.25, 0.64]), surgery (HR = 0.25; 95% CI = [0.12, 0.50]), Luminal A subtype (HR = 0.20; 95% CI = [0.07, 0.53]), and Luminal B subtype (HR = 0.29; 95% CI = [0.10, 0.87]) were related to a reduced MBC-specific death risk. In addition, similar results can be observed in patients with surgery recommended and done ( p < .05). This study may provide evidence for the prevalence trend, cumulative mortality, and death risk of MBC patients.
Long-term efficacy and safety of WovenEndoBridge (WEB)-assisted cerebral aneurysm embolization
Authors: Algin Oktay , Corabay Seniha , Ayberk Gıyas
Published: January 2022

Purpose

Long-term compaction, compression, migration, and recurrence rates of the WovenEndoBridge devices remain unknown. The purpose of this study was to detect these rates and safety profiles of the WovenEndoBridge within 7 years period.

Materials and methods

Eighty-three aneurysms of 79 patients treated with the WovenEndoBridge device were retrospectively evaluated using an occlusion scale (e.g. complete occlusion, neck remnant, and aneurysm remnant) on angiography images.

Results

The residual aneurysm was observed in 11 (13%) aneurysms. The mean and median diameters of the recurrent aneurysms were 6 and 7 mm. Most of the recurrent aneurysms were complex type and/or ruptured. Mean diameters and the neck-to-body ratios of all residual aneurysms in the preoperative imaging exams were above 4 mm and 0.6, respectively. The median values of preoperative height and neck measurements were higher in the recurrent aneurysms than in the adequate occlusion group ( p = 0.006, p = 0.019, respectively). There was a statistically significant positive relationship between preoperative height/neck measurements and the mean diameters of residual aneurysms (rs = 0.32 and p = 0.003; rs = 0.28 and p = 0.011, respectively). The WovenEndoBridge compaction/compression and migration were observed in 5 (45%) and 2 (18%) of the recurrent aneurysms. In 7 (64%) of the residual aneurysms, thrombosed areas were found within the aneurysm. In the follow-up period, four aneurysms (4.8%) were retreated due to widened residual aneurysm. Other aneurysms were improved or stable within 7 years.

Discussion

Our adequate occlusion rate was 87%. Occlusion rates are less favorable than aneurysms with a long height, wide neck, or high neck-to-body ratio. Our study confirms the high safety and efficiency of the WovenEndoBridge. Compaction, compression, and/or migration of the WovenEndoBridge and the presence of intra-aneurysmal thrombosis are the main reasons for the recurrences.
Pattern of change of C-reactive protein levels and its clinical implication in patients with acute poisoning
Authors: Kim Yong Oh , Kim Hyung Il , Jung Bo Kyeung
Published: January 2022

Objectives:

C-reactive protein is well known as an inflammatory indicator in injury, infection, and cancer. However, little is known about its role in poisoning. C-reactive protein levels first increase and then decrease within several days during poisoning management. This study aimed to verify the C-reactive protein change pattern and its clinical co-infection possibility in patients with poisoning.

Methods:

Daily C-reactive protein levels of the patients with poisoning, who were admitted for more than 5 days, were measured. Microbial cultures were conducted, and fever (⩾38°C) and infection-related symptoms were investigated.

Results:

In the enrolled 56 patients, the initial median C-reactive protein levels at hospital day 1, 2, 3, 4, and 5 were 0.28, 4.85, 10.91, 10.57, and 6.68 mg/dL, respectively. C-reactive protein level was the highest at hospital day 3 and decreased thereafter. No statistical difference was observed in the daily and maximal C-reactive protein levels between the culture-positive and culture-negative groups. The levels at hospital days 3–5 and the maximal level were 8.4, 9.2, 5.49, and 11.02 mg/dL, respectively, in non-fever group. The levels at hospital days 3–5 and the maximal level were 7.4, 9.2, 4.74, and 10.81 mg/dL, respectively, in non-symptoms group. Levels at hospital days 3–5 and the maximal level were 5.21, 4.93, 3.7, and 5.28 mg/dL, respectively, in all-negative (culture-negative without fever or infection symptoms) group.

Conclusions:

Acute rise and fall of C-reactive protein levels can be observed in the infection-unlikely patients with poisoning. The levels were similar to bacterial infection levels, possibly due to the drug reaction itself, rather than for superimposed infections.
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

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

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

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

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

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

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

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

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

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

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

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.
A review of menopause nomenclature
Authors: Ambikairajah Ananthan , Walsh Erin , Cherbuin Nicolas
Published: January 2022

Menopause nomenclature varies in the scholarly literature making synthesis and interpretation of research findings difficult. Therefore, the present study aimed to review and discuss critical developments in menopause nomenclature; determine the level of heterogeneity amongst menopause definitions and compare them with the Stages of Reproductive Aging Workshop criteria. Definitions/criteria used to characterise premenopausal and postmenopausal status were extracted from 210 studies and 128 of these studies were included in the final analyses. The main findings were that 39.84% of included studies were consistent with STRAW classification of premenopause, whereas 70.31% were consistent with STRAW classification of postmenopause. Surprisingly, major inconsistencies relating to premenopause definition were due to a total lack of reporting of any definitions/criteria for premenopause (39.84% of studies). In contrast, only 20.31% did not report definitions/criteria for postmenopause. The present findings indicate that there is a significant amount of heterogeneity associated with the definition of premenopause, compared with postmenopause. We propose three key suggestions/recommendations, which can be distilled from these findings. Firstly, premenopause should be transparently operationalised and reported. Secondly, as a minimum requirement, regular menstruation should be defined as the number of menstrual cycles in a period of at least 3 months. Finally, the utility of introducing normative age-ranges as supplementary criterion for defining stages of reproductive ageing should be considered. The use of consistent terminology in research will enhance our capacity to compare results from different studies and more effectively investigate issues related to women’s health and ageing.
Utilization of long acting and permanent contraceptive methods and associated factor among women of reproductive age in west Guji zone, Southwest Ethiopia
Authors: Zeleke Eden Dagnachew , Assefa Dawit Getachew , Woldesenbet Tigist Tekle , Gido Rediet , Mengistu Nebiyu , Molla Wondwosen
Published: January 2022

Background

Increasing access to family planning helps to ensure the reproductive right, decrease unintended pregnancy, improve the health and nutritional status of children, reduction of maternal mortality, and enhance longer birth spacing. However, there is continually low utilization of long acting and permanent contraceptive methods among low and middle-income countries. This study aimed to assess the utilization of long acting and permanent contraceptive methods (LAPMs) and associated factors among women of reproductive age in the West Guji Zone, Ethiopia.

Methods

An institution-based cross-sectional study was carried out among 507 women of reproductive age in the West Guji Zone, Southwest Ethiopia from April 15 to May 15, 2018. Data were collected by a structured, pretested, and interview-based questionnaire with open ended and closed ended questionnaire, then entered, and analyzed by SPSS Version 20. Bivariable and multivariate logistic regression analyses were carried out. A 95% confidence interval (CI) AND P-value < 0.05 was considered to declare statistically significant variables.

Result

The current utilization of LAPMs at West Guji zone among the reproductive-aged group was found to be 51.1%. More than the median of participants had negative altitude (72.4%) and poor knowledge (57%) towards the LAPMs. Educational status of women, the number of alive children, acceptance of utilization of LAPMs, how treated by other staff, and waiting time during service delivery are significant determinant factors of LAPMs.

Conclusion

Overall, more than half of women had a negative attitude and poor knowledge of LAPMs. Educational status of women, the number of alive children, acceptance of utilization of LAPMs, how treated by other staff, and waiting time during service delivery were factors affecting utilization of LAPMs. Therefore, sustained, and appropriate information on LAPMs should be provided to raise knowledge and build the attitude of women and the community. Treating the clients with respect, reducing the waiting time, and collaborative work with health extension worker will enhance utilization of LAPMs.
Upregulation of nuclear factor E2-related factor 2 (Nrf2) represses the replication of herpes simplex virus type 1
Authors: Zhang Li , Wang Jiao , Wang Zhan , Li Ying , Wang Hui , Liu Hongtu
Published: January 2022

Background

Nuclear factor E2-related factor 2 (Nrf2) is an important transcription factor which plays a pivotal role in detoxifying reactive oxygen species (ROS) and has been more recently shown to regulate inflammatory and antiviral responses. However, the role of Nrf2 in Herpes Simplex Virus type 1 (HSV-1) infection is still unclear. In this study, the interaction between the Nrf2 and HSV-1 replication was investigated.

Methods

The levels of oxidative stress was monitored by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) ELISA kits, and the dynamic changes of Nrf2-antioxidant response element (Nrf2-ARE) pathway were detected by Western Blot. The effect of Nrf2-ARE pathway on the regulation of HSV-1 proliferation was analyzed by Western Blot, Real-Time PCR and TCID50assay.

Results

HSV-1 infection induced oxidative stress. Nrf2 was activated, accompanied by the increase of its down-stream antioxidant enzyme heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) in the early stage of HSV-1 infection. The proliferation of HSV-1 was inhibited by overexpression of Nrf2 or treatment with its activator tert-Butylhydroquinone (tBHQ). On the contrary, silencing of Nrf2 promotes virus replication. HO-1 is involved in the regulation of IFN response, leading to efficient anti-HSV-1 effects.

Conclusion

Our observations indicate that the Nrf2-ARE pathway activates a passive defensive response in the early stage of HSV-1 infection. Targeting the Nrf2 pathway demonstrates the potential for combating HSV-1 infection.
Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)
Authors: Glorieux Francis H. , Bonewald Lynda F. , Harvey Nicholas C. , van der Meulen Marjolein C. H.
Published: January 2022

In recent years, much progress has been made in understanding the mechanisms of bone growth and development over a lifespan, including the crosstalk between muscle and bone, to achieve optimal structure and function. While there have been significant advances in understanding how to help improve and maintain bone health in normal individuals, there is limited knowledge on whether these mechanisms apply or are compromised in pathological states. X-linked hypophosphatemia (XLH) (ORPHA:89936) is a rare, heritable, renal phosphate-wasting disorder. The resultant chronic hypophosphatemia leads to progressive deterioration in musculoskeletal function, including impaired growth, rickets, and limb deformities in children, as well as lifelong osteomalacia with reduced bone quality and impaired muscle structure and function. The clinical manifestations of the disease vary both in presentation and severity in affected individuals, and many of the consequences of childhood defects persist into adulthood, causing significant morbidity that impacts physical function and quality of life. Intervention to restore phosphate levels early in life during the critical stages of skeletal development in children with XLH could optimize growth and may prevent or reduce bone deformities in childhood. A healthier bone structure, together with improved muscle function, can lead to physical activity enhancing musculoskeletal health throughout life. In adults, continued management may help to maintain the positive effects acquired from childhood treatment, thereby slowing or halting disease progression. In this review, we summarize the opinions from members of a working group with expertise in pediatrics, epidemiology, and bone, joint and muscle biology, on potential outcomes for people with XLH, who have been optimally treated from an early age and continue treatment throughout life.
Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis
Authors: Wang Hui , Ma Zeng-Hui , Xu Ling-Zi , Yang Liu , Ji Zhao-Zheng , Tang Xin-Zhou , Liu Jing-Ran , Li Xue , Cao Qing-Jiu , Liu Jing
Published: January 2022

Background

Structural magnetic resonance imaging (sMRI) studies have shown atypicalities in structural brain changes in individuals with autism spectrum disorder (ASD), while a noticeable discrepancy in their results indicates the necessity of conducting further researches.

Methods

The current study investigated the atypical structural brain features of autistic individuals who aged 6–30 years old. A total of 52 autistic individuals and 50 age-, gender-, and intelligence quotient (IQ)-matched typically developing (TD) individuals were included in this study, and were assigned into three based cohorts: childhood (6–12 years old), adolescence (13–18 years old), and adulthood (19–30 years old). Analyses of whole-brain volume and voxel-based morphometry (VBM) on the sMRI data were conducted.

Results

No significant difference was found in the volumes of whole-brain, gray matter, and white matter between the autism and TD groups in the three age-based cohorts. For VBM analyses, the volumes of gray matter in the right superior temporal gyrus and right inferior parietal lobule in the autism group (6–12 years old) were smaller than those in the TD group; the gray matter volume in the left inferior parietal lobule in the autism group (13–18 years old) was larger than that in the TD group; the gray matter volume in the right middle occipital gyrus in the autism group (19–30 years old) was larger than that in the TD group, and the gray matter volume in the left posterior cingulate gyrus in the autism group was smaller than that in the TD group.

Conclusion

Autistic individuals showed different atypical regional gray matter volumetric changes in childhood, adolescence, and adulthood compared to their TD peers, indicating that it is essential to consider developmental stages of the brain when exploring brain structural atypicalities in autism.
Study protocol for comparing Screening, Brief Intervention, and Referral to Treatment (SBIRT) to referral as usual for depression in African American churches
Authors: Hankerson Sidney H. , Shelton Rachel , Weissman Myrna , Wells Kenneth B. , Teresi Jeanne , Mallaiah Janhavi , Joshua Amita , Williams Olajide
Published: January 2022

Background

Depression is a leading cause of disability worldwide. African American adults, compared to White adults, are half as likely to be screened for depression in primary care settings. Disparities in depression screening contribute to poor clinical outcomes, as African Americans with depression are more disabled and sicker longer compared to Whites. African American churches are trusted settings that provide access to supports for depression. Indeed, in the first study of its kind, the investigators found that 20% of adults in African American churches screened positive for depression using the Patient Health Questionnaire-9 (PHQ-9). However, no subjects with a positive screen (PHQ-9 ≥ 10) accepted a treatment referral when offered by research personnel. Community Health Workers, who are trusted paraprofessionals from the target community, may bridge the gap between depression screening and treatment. The investigators have trained and certified 112 Community Health Workers from 45 African American churches in New York City to deliver an evidence-based intervention called Screening, Brief Intervention, and Referral to Treatment (SBIRT). Thus, the aim of the current study is to test the impact of Community Health Worker-delivered depression screening in Black churches on engagement with clinical services.

Methods

Using a hybrid type 1 effectiveness-implementation design, we propose a 2-arm, mixed-methods cluster randomized controlled trial. Church study sites will be randomized to either SBIRT (intervention arm) or referral as usual (usual care arm). This trial will be conducted with 600 church members across 30 churches (300 intervention; 300 usual care). Our primary outcome is treatment engagement, defined as attending a depression-related clinical visit. Secondary outcomes will be changes in Mental Health-Related Quality of Life and depressive symptoms at 3 and 6 months post-screening. Lastly, we will conduct a concurrent, mixed-methods (qualitative-quantitative) process evaluation to assess contextual facilitators and barriers of screening and referral.

Discussion

This is the first randomized trial of a church-placed, community health worker-delivered intervention for depression in African American populations. This study may provide a novel and effective approach to increasing depression identification and treatment linkage in economically disadvantaged populations with high depression rates.

Trial registration

ClinicalTrials.govNCT04524767. Registered on 21 August 2020.
Monitoring insecticide resistance of adult and larval Aedes aegypti (Diptera: Culicidae) in Phnom Penh, Cambodia
Authors: Boyer Sebastien , Maquart Pierre-Olivier , Chhuoy Kalyan , Suor Kimhuor , Chhum Moeun , Heng Kimly , Leng Sokkeang , Fontenille Didier , Marcombe Sebastien
Published: January 2022

Background

Dengue fever is a major public health concern in Cambodia, with thousands of cases every year in urban, suburban and rural areas of the country. The main vector of dengue fever in Cambodia is Aedes aegypti. The organophosphate larvicide temephos and adulticides belonging to the pyrethroid family have been widely used for decades by public health authorities to fight dengue vectors, but resistance of Ae. aegypti to these insecticides has been previously described for Cambodia.

Methods

In order to adapt the vector control strategy presently used in Cambodia, we tested 14 adulticides belonging to the carbamate, organochlorine, organophosphate, and pyrethroid insecticide families and three larvicides [temephos, spinosad and Bacillus thuringiensis ser. israelensis (Bti)] belonging to three different insecticide families (organophosphates, spinosyns and entomopathogenic bacteria). The standard procedures used here to test the adults and larvae of an Ae. aegypti population from Phnom Penh followed World Health Organization guidelines.

Results

For adults, high mortality rates were observed with carbamate, organophosphate and organochlorine (with the exception of dichlorodiphenyltrichloroethane) insecticides (i.e. between 87.6 and 100%), while low mortality rates were observed with all of the tested pyrethroid insecticides (i.e. between 1 and 35%). For larvae, no resistance against Bti was detected [resistance ratio (RR90 < 1.6)], but moderate resistance was observed for temephos and spinosad (RR90 < 5.6).

Conclusions

The results of this study indicate that (i) Bti should be considered a serious alternative to temephos for the control of Ae. aegypti larvae; and (ii) the carbamate adulticides propoxur and bendiocarb should be employed instead of the widely used pyrethroid insecticides for the control of adult Ae. aegypti on land under mosaic farming and crop rotation in Cambodia, as the insects were found to be resistant to the latter types of insecticide. Research focusing on insecticide resistance and innovative and effective vector control strategies should be undertaken as a public health priority in Cambodia.

Graphical abstract