bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors of time to first abortion after sexual debut among fragile state Congolese women: a survival analysis
Authors: Ekholuenetale Michael , Ekholuenetale Charity Ehimwenma , Barrow Amadou
Published: March 2021

Background

Despite the common restrictive abortion laws, abortion remains widespread in sub-Saharan Africa (SSA) countries. Women still utilize abortion services and put their lives and health at risk because abortion can only be procured illegally in private facilities such as mid-level or small patent medicine store that may be manned by unskilled providers or through a non-medicated approach. The objective of this study was to investigate the prevalence of abortion, the reasons women had abortions, median years to first abortion after sexual debut and examine the factors of time to first abortion among women of reproductive age in the Republic of Congo.

Methods

We used data from the most recent Republic of Congo Demographic and Health Survey (DHS). A total sample of 3622 women aged 15–49 years was analyzed. We estimated the overall prevalence of abortion and median years to first abortion. Furthermore, we examined the factors of time to first abortion after sexual debut using multivariable Cox regression and reported the estimates using adjusted Hazard Ratio (aHR) and 95% confidence intervals (CI). Statistical significance was determined at p < 0.05.

Results

60% of pregnancies which are terminated are as a result of induced abortion and median years of time to first abortion after sexual debut was 9.0. The prominent reasons for abortion were due to too short birth interval (23.8%), lack of money (21.0%) and that husband/partner did not need a child at that time (14.0%). Women’s age and region were notable factors in timing to first abortion. Furthermore, women from poorer, middle, richer and richest households had 34, 67, 86 and 94% higher risk of abortion respectively, when compared with women from poorest households (all p < 0.05). Women currently in union/living with a man and formerly in union had 41 and 29% reduction in the risk of abortion respectively, when compared with those never in union (all p < 0.05). In addition, women with primary and secondary+ education had 42 and 76% higher risk of abortion respectively, when compared with women with no formal education (all p < 0.05).

Conclusion

There was high prevalence of abortion with short years at first abortion. Abortion was associated with women’s characteristics. There is need for unwanted pregnancy prevention intervention and the improvement in pregnancy care to reduce adverse pregnancy outcomes among women.
Extended field-of-view ultrasound imaging is reliable for measuring Transversus Abdominis muscle size at rest and during contraction
Authors: Johnson A. Wayne , Adams Lauren , Kho Jade B. , Green Daniel M. , Pace Nicolas B. , Mitchell Ulrike H.
Published: March 2021

Background

The strength and size of core muscles, including the abdominal muscles, are crucial to proper function in most activities. Therefore, it is important to reliably assess these characteristics. Our primary objective was to determine if the length, thickness and cross-sectional area of the transversus abdominis (TrA) can be visualized independently from the internal and external abdominal oblique muscles using extended field of view ultrasound imaging at rest and with contraction and to establish its intra- and inter-tester reliability.

Methods

Twenty-six individuals were recruited to participate in the study (20 F, 6 M), average age 24.0 years (SD 9.4), height 170.7 cm (SD 8.6) and weight 63.9 kg (SD 9.0). From this total number of participants, two groups of 16 randomly selected participants were assessed to determine intra- and inter-tester reliability respectively. Extended field of view ultrasound images were obtained at three vertebral levels during rest and contraction in the side lying position for both the right and left sides of the trunk.

Results

Excellent intra-tester and inter-tester reliability was seen (ICC range of 0.972 to 0.984). The overall average percent standard error of the measurement for all measurements and locations was approximately 4%. The overall average minimal difference for the thickness measurement for the resting and contraction conditions combined were as follows: intratester 0.056 (0.014) cm and intertester 0.054 (0.017) cm, for area intratester 0.287 (0.086) cm2 and intertester 0.289 (0.101) cm2 and for length intratester 0.519 (0.097) cm and intertester 0.507 (0.085) cm.

Conclusions

Extended field of view ultrasound imaging is an effective method of reliably capturing clear images of the TrA during rest and contraction. It provides an efficient mechanism for the analysis of muscle morphology by being able to measure the cross-sectional area, thickness, and length on one image. This methodology is recommended for studies investigating TrA function and training.
Comparative short-term outcomes of enhanced recovery after surgery (ERAS) program and non-ERAS traditional care in elderly patients undergoing lumbar arthrodesis: a retrospective study
Authors: Li Zhong-En , Lu Shi-Bao , Kong Chao , Sun Wen-Zhi , Wang Peng , Zhang Si-Tao
Published: March 2021

Background

Enhanced recovery after surgery (ERAS) program is an evidence-based improvement over non-ERAS traditional care. The aim of the present study was to analyze the safety, feasibility, and efficacy of an ERAS program in patients over 70 years undergoing lumbar arthrodesis by comparison with non-ERAS traditional care.

Methods

During January 2018 to December 2018, patients enrolled received non-ERAS traditional care, while the ERAS program was implemented from January to December 2019. Demographic characteristics, comorbidities, surgical data and postoperative recovery parameters were collected from all patients. Postoperative pain scores were evaluated by visual analog scales (VAS). The clinical outcomes were length of stay (LOS), postoperative complications and postoperative pain scores. Compliance results were also collected.

Result

A total of 127 patients were enrolled, including 67 patients in the non-ERAS traditional care group and 60 patients in the ERAS group. The demographic characteristics and comorbidities of the two groups showed no significant differences. The LOS of patients treated with ERAS program (13.6 ± 4.0 days) was significantly less than that of patients treated with non-ERAS traditional care (15.6 ± 3.9 days) (p = 0.034). Complication rate was 8.3% in the ERAS group versus 20.9% in the non-ERAS traditional care group (p = 0.048). VAS (back) in the ERAS group was significantly lower on postoperative day (POD) 1 and POD2. Postoperative recovery parameters were improved in the ERAS group. The overall compliance with the ERAS program was 94%.

Conclusions

Based on our results, ERAS program is safer and more effective for elderly patients over 70 undergoing lumbar arthrodesis than non-ERAS traditional care.
Optimizations for identifying reference genes in bone and cartilage bioengineering
Authors: Xiong Fei , Cheng Xiangyun , Zhang Chao , Klar Roland Manfred , He Tao
Published: March 2021

Background

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) remains one of the best-established techniques to assess gene expression patterns. However, appropriate reference gene(s) selection remains a critical and challenging subject in which inappropriate reference gene selction can distort results leading to false interpretations. To date, mixed opinions still exist in how to choose the most optimal reference gene sets in accodrance to the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guideline. Therefore, the purpose of this study was to investigate which schemes were the most feasible for the identification of reference genes in a bone and cartilage bioengineering experimental setting. In this study, rat bone mesenchymal stem cells (rBMSCs), skeletal muscle tissue and adipose tissue were utilized, undergoing either chondrogenic or osteogenic induction, to investigate the optimal reference gene set identification scheme that would subsequently ensure stable and accurate interpretation of gene expression in bone and cartilage bioengineering.

Results

The stability and pairwise variance of eight candidate reference genes were analyzed using geNorm. The V0.15- vs. Vmin-based normalization scheme in rBMSCs had no significant effect on the eventual normalization of target genes. In terms of the muscle tissue, the results of the correlation of NF values between the V0.15 and Vmin schemes and the variance of target genes expression levels generated by these two schemes showed that different schemes do indeed have a significant effect on the eventual normalization of target genes. Three selection schemes were adopted in terms of the adipose tissue, including the three optimal reference genes (Opt3), V0.20 and Vmin schemes, and the analysis of NF values with eventual normalization of target genes showed that the different selection schemes also have a significant effect on the eventual normalization of target genes.

Conclusions

Based on these results, the proposed cut-off value of Vn/n + 1 under 0.15, according to the geNorm algorithm, should be considered with caution. For cell only experiments, at least rBMSCs, a Vn/n + 1 under 0.15 is sufficient in RT-qPCR studies. However, when using certain tissue types such as skeletal muscle and adipose tissue the minimum Vn/n + 1 should be used instead as this provides a far superior mode of generating accurate gene expression results. We thus recommended that when the stability and variation of a candidate reference genes in a specific study is unclear the minimum Vn/n + 1 should always be used as this ensures the best and most accurate gene expression value is achieved during RT-qPCR assays.
Analysis of the relationship between periodontitis and osteoporosis/fractures: a cross-sectional study
Authors: Hong Seok-Jin , Yang Byoung-Eun , Yoo Dae-Myoung , Kim Sung-Jae , Choi Hyo-Geun , Byun Soo-Hwan
Published: March 2021

Background

Chronic periodontitis is a multifactorial inflammatory disease resulting in patients exhibiting high levels of inflammatory factors causing systemic inflammatory bone destruction that may lead to osteoporosis development. The association between periodontitis and osteoporosis has been documented; however, the findings remain unclear. This study aimed to identify the association between periodontitis and osteoporosis using a cross-sectional study design and Korean Genome and Epidemiology Study (KoGES) health examinee data.

Methods

This cross-sectional study used epidemiological data from the KoGES during 2004–2016. Of 125,324 participants (age, 40–79 years), 9969 with periodontitis and 115,332 controls (without periodontitis) were selected. We analyzed the history of osteoporosis and fractures of all participants. All participants were examined according to age, sex, income group, obesity, smoking habits, alcohol consumption, and food intake. To analyze the odds ratio (OR) of periodontitis for those with osteoporosis and fractures, a logistic regression model was used.

Results

The adjusted odds ratio (aOR) of periodontitis for osteoporosis was 2.16 (95% confidence interval [CI], 2.01–2.31;P < 0.001). The aOR of periodontitis for any fracture was 1.54 (95% CI 1.46–1.62;P < 0.001).

Conclusion

Osteoporosis and fractures are associated with periodontitis. Performing regular oral hygiene and examinations of bone mineral density are recommended to prevent aggravation of osteoporosis and periodontitis.
An ecological study on the association between universal health service coverage index, health expenditures, and early childhood caries
Authors: Folayan Morenike Oluwatoyin , Tantawi Maha El , Virtanen Jorma I. , Feldens Carlos Alberto , Rashwan Maher , Kemoli Arthur M. , Villena Rita , Al-Batayneh Ola B. , Amalia Rosa , Gaffar Balgis , Mohebbi Simin Z. , Arheiam Arheiam , Daryanavard Hamideh , Vukovic Ana , Schroth Robert J. ,   for the Early Childhood Caries Advocacy Group
Published: March 2021

Background

Universal health care (UHC) may assist families whose children are most prone to early childhood caries (ECC) in accessing dental treatment and prevention. The purpose of this study was to determine the association between UHC, health expenditure and the global prevalence of ECC.

Methods

Health expenditure as percentage of gross domestic product, UHC service coverage index, and the percentage of 3–5-year-old children with ECC were compared among countries with various income levels using one-way analysis of variance (ANOVA). Three linear regression models were developed, and each was adjusted for the country income level with the prevalence of ECC in 3–5-year-old children being the dependent variable. In model 1, UHC service coverage index was the independent variable whereas in model 2, the independent variable was the health expenditure as percentage of GDP. Model 3 included both independent variables together. Regression coefficients (B), 95% confidence intervals (CIs), P values, and partial eta squared (ƞ2) as measure of effect size were calculated.

Results

Linear regression including both independent factors revealed that health expenditure as percentage of GDP (P < 0.0001) was significantly associated with the percentage of ECC in 3–5-year-old children while UHC service coverage index was not significantly associated with the prevalence of ECC (P = 0.05). Every 1% increase in GDP allocated to health expenditure was associated with a 3.7% lower percentage of children with ECC (B = − 3.71, 95% CI: − 5.51, − 1.91). UHC service coverage index was not associated with the percentage of children with ECC (B = 0.61, 95% CI: − 0.01, 1.23). The impact of health expenditure on the prevalence of ECC was stronger than that of UHC coverage on the prevalence of ECC (ƞ2 = 0.18 vs. 0.05).

Conclusions

Higher expenditure on health care may be associated with lower prevalence of ECC and may be a more viable approach to reducing early childhood oral health disparities than UHC alone. The findings suggest that currently, UHC is weakly associated with lower global prevalence of ECC.
Exploring why medical students still feel underprepared for clinical practice: a qualitative analysis of an authentic on‐call simulation
Authors: Hawkins Nichola , Younan Helen-Cara , Fyfe Molly , Parekh Ravi , McKeown Andrew
Published: March 2021

Background

Current research shows that many UK medical graduates continue to feel underprepared to work as a junior doctor. Most research in this field has focused on new graduates and employed the use of retrospective self-rating questionnaires. There remains a lack of detailed understanding of the challenges encountered in preparing for clinical practice, specifically those faced by medical students, where relevant educational interventions could have a significant impact. Through use of a novel on-call simulation, we set out to determine factors affecting perceived preparation for practice in final year medical students and identify ways in which we may better support them throughout their undergraduate training.

Methods

30 final year medical students from Imperial College London participated in a 90-minute simulation on hospital wards, developed to recreate a realistic on-call experience of a newly qualified doctor. Students partook in pairs, each observed by a qualified doctor taking field notes on their decisions and actions. A 60-minute semi-structured debrief between observer and student pair was audio-recorded for analysis. Field notes and students’ clinical documentation were used to explore any challenges encountered. Debrief transcripts were thematically analysed through a general inductive approach. Cognitive Load Theory (CLT) was used as a lens through which to finalise the evolving themes.

Results

Six key themes emerged from the on-call simulation debriefs: information overload, the reality gap, making use of existing knowledge, negative feelings and emotions, unfamiliar surroundings, and learning ‘on the job’.

Conclusions

The combination of high fidelity on-call simulation, close observation and personalised debrief offers a novel insight into the difficulties faced by undergraduates in their preparation for work as a junior doctor. In using CLT to conceptualise the data, we can begin to understand how cognitive load may be optimised within this context and, in doing so, we highlight ways in which undergraduate curricula may be adapted to better support students in their preparation for clinical practice. Recommendations are centred around enhancing the expertise of the learner through ‘whole task’ training approaches and integrated learning, as well as navigating negative emotions and supporting lifelong ‘learning while working’.
A systematic review of theoretical constructs in CDS literature
Authors: Liu Siru , Reese Thomas J. , Kawamoto Kensaku , Del Fiol Guilherme , Weir Charlene
Published: March 2021

Background

Studies that examine the adoption of clinical decision support (CDS) by healthcare providers have generally lacked a theoretical underpinning. The Unified Theory of Acceptance and Use of Technology (UTAUT) model may provide such a theory-based explanation; however, it is unknown if the model can be applied to the CDS literature.

Objective

Our overall goal was to develop a taxonomy based on UTAUT constructs that could reliably characterize CDS interventions.

Methods

We used a two-step process: (1) identified randomized controlled trials meeting comparative effectiveness criteria, e.g., evaluating the impact of CDS interventions with and without specific features or implementation strategies; (2) iteratively developed and validated a taxonomy for characterizing differential CDS features or implementation strategies using three raters.

Results

Twenty-five studies with 48 comparison arms were identified. We applied three constructs from the UTAUT model and added motivational control to characterize CDS interventions. Inter-rater reliability was as follows for model constructs: performance expectancy (κ = 0.79), effort expectancy (κ = 0.85), social influence (κ = 0.71), and motivational control (κ = 0.87).

Conclusion

We found that constructs from the UTAUT model and motivational control can reliably characterize features and associated implementation strategies. Our next step is to examine the quantitative relationships between constructs and CDS adoption.
Clinical analysis and long-term treatment monitoring of 3 patients with glycogen storage disease type Ib
Authors: Du Caiqi , Li Zhuoguang , Wei Hong , Zhang Min , Hu Minghui , Zhang Cai , Luo Xiaoping , Liang Yan
Published: March 2021

Background

To investigate the clinical and genetic characteristics of patients with glycogen storage disease type Ib (GSD Ib).

Case presentation

This report retrospectively analyzed the clinical data of 3 patients with GSD Ib admitted into our hospital, and summarized their onset characteristics, clinical manifestations, related examinations and treatment as well as mutational spectrum. After gene sequencing, the diagnosis of GSD Ib was confirmed in all 3 patients. Five variants of SLC37A4 gene were detected, of which c. 572C > T was the common variant and c. 680G > A was a novel variant. The 3 cases of GSD Ib were mainly affected by liver enlargement, growth retardation, etc., and all had a history of repeated infections. At the onset, patients mainly manifested as mildly elevated alanine-aminotransferase (ALT), accompanied by decreased absolute neutrophil count (ANC), hypertriglyceridemia, and metabolic disorders (hypoglycemia, hyperlactic acidemia, metabolic acidosis, etc.). After long-term treatment by oral uncooked cornstarch, the abnormal liver enzymes gradually returned to normal, and metabolic abnormalities were basically controlled most of the time. With increasing age, ANC of 2 patients decreased progressively, whereas the times of infections was reduced.

Conclusions

We reported 3 cases with GSD Ib and a novel SLC37A4 variant. The possibility of GSD type Ib should be kept on alert when a patient suffers recurrent infections, accompanied by hepatomegaly, elevated liver enzymes, hypoglycemia, dyslipidemia, and metabolic disorders.
Combined genomic and proteomic approaches reveal DNA binding sites and interaction partners of TBX2 in the developing lung
Authors: Lüdtke Timo H. , Wojahn Irina , Kleppa Marc-Jens , Schierstaedt Jasper , Christoffels Vincent M. , Künzler Patrick , Kispert Andreas
Published: March 2021

Background

Tbx2encodes a transcriptional repressor implicated in the development of numerous organs in mouse. During lung development TBX2 maintains the proliferation of mesenchymal progenitors, and hence, epithelial proliferation and branching morphogenesis. The pro-proliferative function was traced to direct repression of the cell-cycle inhibitor genesCdkn1aandCdkn1b, as well as of genes encoding WNT antagonists,FrzbandShisa3,to increase pro-proliferative WNT signaling. Despite these important molecular insights, we still lack knowledge of the DNA occupancy of TBX2 in the genome, and of the protein interaction partners involved in transcriptional repression of target genes.

Methods

We used chromatin immunoprecipitation (ChIP)-sequencing and expression analyses to identify genomic DNA-binding sites and transcription units directly regulated by TBX2 in the developing lung. Moreover, we purified TBX2 containing protein complexes from embryonic lung tissue and identified potential interaction partners by subsequent liquid chromatography/mass spectrometry. The interaction with candidate proteins was validated by immunofluorescence, proximity ligation and individual co-immunoprecipitation analyses.

Results

We identifiedIl33andCcn4as additional direct target genes of TBX2 in the pulmonary mesenchyme. Analyzing TBX2 occupancy data unveiled the enrichment of five consensus sequences, three of which match T-box binding elements. The remaining two correspond to a high mobility group (HMG)-box and a homeobox consensus sequence motif. We found and validated binding of TBX2 to the HMG-box transcription factor HMGB2 and the homeobox transcription factor PBX1, to the heterochromatin protein CBX3, and to various members of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex including HDAC1, HDAC2 and CHD4.

Conclusion

Our data suggest that TBX2 interacts with homeobox and HMG-box transcription factors as well as with the NuRD chromatin remodeling complex to repress transcription of anti-proliferative genes in the pulmonary mesenchyme.
Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death
Authors: Wang Hengxu , Wang Zhigang , Xu Weihui , Wang Kexin
Published: March 2021

Background

Myriocin is a natural product with antifungal activity and is derived from Bacillus amyloliquefaciens LZN01. Our previous work demonstrated that myriocin can inhibit the growth of Fusarium oxysporum f. sp. niveum (Fon) by inducing membrane damage. In this study, the antifungal actions of myriocin against Fon were investigated with a focus on the effects of myriocin on intracellular molecules.

Results

Analysis of DNA binding and fluorescence spectra demonstrated that myriocin can interact with dsDNA from Fon cells. The intracellular-targeted mechanism of action was also supported by transcriptomic and proteomic analyses; a total of 2238 common differentially expressed genes (DEGs) were identified. The DEGs were further verified by RT-qPCR. Most of the DEGs were assigned metabolism and genetic information processing functions and were enriched in ribosome biogenesis in eukaryotes pathway. The expression of some genes and proteins in ribosome biogenesis in eukaryotes pathway was affected by myriocin, primarily the genes controlled by the C6 zinc cluster transcription factor family and the NFYA transcription factor. Myriocin influenced the posttranscriptional processing of gene products by triggering the main RI (retained intron) events of novel alternative splicing; myriocin targeted key genes (FOXG_09470) or proteins (RIOK2) in ribosome biogenesis in eukaryotes pathway, resulting in disordered translation.

Conclusions

In conclusion, myriocin was determined to exhibit activity against Fon by targeting intracellular molecules. The results of our study may help to elucidate the antifungal actions of myriocin against Fon.
Enhanced ascomycin production in Streptomyces hygroscopicus var. ascomyceticus by employing polyhydroxybutyrate as an intracellular carbon reservoir and optimizing carbon addition
Authors: Wang Pan , Yin Ying , Wang Xin , Wen Jianping
Published: March 2021

Background

Ascomycin is a multifunctional antibiotic produced by Streptomyces hygroscopicus var. ascomyceticus. As a secondary metabolite, the production of ascomycin is often limited by the shortage of precursors during the late fermentation phase. Polyhydroxybutyrate is an intracellular polymer accumulated by prokaryotic microorganisms. Developing polyhydroxybutyrate as an intracellular carbon reservoir for precursor synthesis is of great significance to improve the yield of ascomycin.

Results

The fermentation characteristics of the parent strain S. hygroscopicus var. ascomyceticus FS35 showed that the accumulation and decomposition of polyhydroxybutyrate was respectively correlated with cell growth and ascomycin production. The co-overexpression of the exogenous polyhydroxybutyrate synthesis gene phaC and native polyhydroxybutyrate decomposition gene fkbU increased both the biomass and ascomycin yield. Comparative transcriptional analysis showed that the storage of polyhydroxybutyrate during the exponential phase accelerated biosynthesis processes by stimulating the utilization of carbon sources, while the decomposition of polyhydroxybutyrate during the stationary phase increased the biosynthesis of ascomycin precursors by enhancing the metabolic flux through primary pathways. The comparative analysis of cofactor concentrations confirmed that the biosynthesis of polyhydroxybutyrate depended on the supply of NADH. At low sugar concentrations found in the late exponential phase, the optimization of carbon source addition further strengthened the polyhydroxybutyrate metabolism by increasing the total concentration of cofactors. Finally, in the fermentation medium with 22 g/L starch and 52 g/L dextrin, the ascomycin yield of the co-overexpression strain was increased to 626.30 mg/L, which was 2.11-fold higher than that of the parent strain in the initial medium (296.29 mg/L).

Conclusions

Here we report for the first time that polyhydroxybutyrate metabolism is beneficial for cell growth and ascomycin production by acting as an intracellular carbon reservoir, stored as polymers when carbon sources are abundant and depolymerized into monomers for the biosynthesis of precursors when carbon sources are insufficient. The successful application of polyhydroxybutyrate in increasing the output of ascomycin provides a new strategy for improving the yields of other secondary metabolites.
miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer
Authors: Zhang Wenjing , Yang Haitao , Wang Zhongqiu , Wu Yanting , Wang Jingzhai , Duan Guihua , Guo Qiang , Zhang Yu
Published: March 2021

Background

Transcription factors (TFs) may be engaged in reciprocal regulatory circuits with certain miRNAs to maintain cellular homeostasis. Disequilibrium of the reciprocities by certain tumor-related stimuli may give rise to deregulation of downstream cellular signaling pathways, thus promoting malignant tumor phenotypes. Specificity Protein 1 (SP1) is the most representative member of the tumor-related transcription factors. Previous studies disclosed that SP1 can transcriptionally regulate miRNAs and coding genes to facilitate tumor progression. In our study, we used bioinformatic analysis to predict several SP1-binding sites within the miR-320a promoter and found that SP1 is a predicted target gene of miR-320a. Therefore, we hypothesize a reciprocal regulatory link between SP1 and miR-320a that participates in colorectal cancer (CRC) development

Methods

We performed bioinformatic analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, dual-luciferase reporter assays, and a series of in vitro and in vivo functional assays to describe a novel SP1/miR-320a reciprocal interaction in CRC

Results

First, we found that miR-320a was significantly downregulated in CRC tissues and cell lines. Consistent with findings in other cancers, miR-320a exhibited inhibitory effects on cell growth and invasion of CRC in vitro and in vivo. Moreover, we identified SP1 as a target gene of miR-320a, and ectopic SP1 expression partly abolished miR-320a-induced inhibitory effects. Conversely, we confirmed that SP1 interacts with the miR-320a promoter, leading to depression of miR-320a. This illustrates a double-negative feedback loop between miR-320a and SP1. Additionally, based on the fact that SP1 promotes MACC1 transcription, we determined via immunoblotting that the oncogenic MACC1/MET signaling pathway was inactivated in the context of miR-320a-induced SP1 downregulation

Conclusion

Taken together, our study is the first to describe a miR-320a/SP1 negative reciprocal interaction, which contributes to cell growth and invasion in CRC through modulation of the MACC1/MET signaling pathway.
Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria
Authors: Fraser Keith J. , Mwandigha Lazaro , Traore Sekou F. , Traore Mohamed M. , Doumbia Seydou , Junnila Amy , Revay Edita , Beier John C. , Marshall John M. , Ghani Azra C. , Müller Gunter
Published: March 2021

Background

Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes.

Methods

It was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs.

Results

The entomological study showed a significant reduction of ~ 57% (95% CI 33–72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75–100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07–0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28–0.38 per day).

Conclusions

From epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.
Temporal evolution of sulfadoxine-pyrimethamine resistance genotypes and genetic diversity in response to a decade of increased interventions against Plasmodium falciparum in northern Ghana
Authors: Amenga-Etego Lucas N. , Asoala Victor , Agongo Godfred , Jacob Christopher , Goncalves Sonia , Awandare Gordon A. , Rockett Kirk A. , Kwiatkowski Dominic
Published: March 2021

Background

Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana.

Methods

A total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for pfdhfr and pfdhps genes and the combined pfhdfr/pfdhps genes across all years.

Results

At the pfdhfr locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants (IRNI) were detected from 2009 to 2018. Two double mutant haplotypes (NRNI and ICNI) were found, with haplotype NRNI having a much higher prevalence (average 13.8%) than ICNI (average 3.2%) across all years. Six pfdhps haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a pfdhps double mutant (AGKAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes, pfdhfr/pfdhps combined triple (NRNI + AAKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple (IRNI + AAKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple (IRNI + AGKAA or SGEAA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons.

Conclusions

Despite high prevalence of pfdhfr triple mutants and combined pfdhfr/pfdhps quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.
Validation of living with chronic illness scale in a type 2 diabetes mellitus population
Authors: Caro-Bautista Jorge , Rodríguez-Blázquez Carmen , Perez-Manchon David , Timonet-Andreu Eva , Carvajal-Carrascal Gloria , Fuentes-Ramírez Alejandra , Corchon Silvia , Aranda-Gallardo Marta , Ambrosio Leire
Published: March 2021

Background

Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population.

Methods

In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis. The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument.

Results

The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values < ½SD = 8.52) and correlates positively with social support (DUFSS) (rs = 0.56), quality of life (WHOQOL-BREF) (rs = 0.51–0.30) and ssatisfaction with life (SLS-6) (rs = 0.50–0.38). The original 26-items version of the scale did not support totally the confirmatory factor analysis. The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for structural validity.

Conclusions

The LW-CI-T2DM is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.
The path linking disease severity and cognitive function with quality of life in Parkinson’s disease: the mediating effect of activities of daily living and depression
Authors: He Yao , Tian Yuling , Han Hongjuan , Cui Jing , Ge Xiaoyan , Qin Yao , Luo Yanhong , Bai Wenlin , Yu Hongmei
Published: March 2021

Background

Research on quality of life (QOL) with Parkinson’s disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence.

Methods

We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and the physical health and mental health component summary scores measured by the SF36 quality of life instrument.

Results

There was a significant mediating effect of PD severity on physical health via ADL and depression (95% CI: − 0.669, − 0.026), and a significant direct effect (p < 0.001). The mediating effect of PD severity on mental health via ADL and depression was significant (95% CI: − 2.135, − 0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on physical health via ADL and depression (95% CI: 0.025, 0.219) and a significant direct effect (p < 0.001). The mediating effect of cognitive function on mental health via ADL and depression was significant (95% CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The physical health models showed a partial mediation, and the mental health models showed a complete mediation, of ADL and depression.

Conclusions

PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect physical health and mental health through different pathways.
Volume and accumulation patterns of physical activity and sedentary time: longitudinal changes and tracking from early to late childhood
Authors: Downing Katherine L , Hinkley Trina , Timperio Anna , Salmon Jo , Carver Alison , Cliff Dylan P , Okely Anthony D , Hesketh Kylie D
Published: March 2021

Background

Physical activity (PA) decreases and sedentary time (SED) increases across childhood, with both behaviours tracking. However, no studies have examined how accumulation patterns of PA and SED (i.e., prolonged bouts, frequency of breaks in sedentary time) change and track over time. The aim of this study was to investigate longitudinal changes in and tracking of total volume and accumulation patterns of SED, light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA) among boys and girls.

Methods

In 2008/09 (T1), children in HAPPY (3-5y; n = 758) in Melbourne, Australia wore ActiGraph GT1M accelerometers to objectively assess SED, LPA, MPA and VPA. This was repeated at age 6-8y (T2; n = 473) and 9-11y (T3; n = 478). Ten pattern variables were computed: bouts of ≥ 5-, ≥ 10-, ≥ 15- and ≥ 20-min for SED, ≥ 1- and ≥ 5-min for LPA, ≥ 1-min for MPA, ≥ 1- and ≥ 5-min for VPA, and breaks in SED (interruptions of > 25 counts 15 s− 1). Longitudinal mixed models examined changes from T1-3, controlling for T1 age. Generalized estimating equations assessed tracking over the three time points, controlling for T1 age and time between measurements. Analyses were stratified by sex.

Results

Total volume and bouts of SED and SED breaks increased, while total volume and bouts of LPA decreased for both sexes. There was a small decrease in total volume of MPA for girls, but time spent in ≥ 1-min bouts increased for both sexes. Total volume of VPA increased for both sexes, with time spent in ≥ 1-min bouts increasing for boys only. All volume and pattern variables tracked moderately for boys, except for all SED bouts ≥ 15-min, LPA bouts ≥ 5-min and MPA bouts ≥ 1-min (which tracked weakly). For girls, total SED and SED bouts ≥ 1-min tracked strongly, total volume of LPA, MPA and VPA, ≥ 5- and ≥ 10-min SED bouts, and ≥ 1-min LPA and MPA bouts tracked moderately, and SED breaks, all SED bouts ≥ 15 min, LPA bouts ≥ 5 min and all VPA bouts tracked weakly.

Conclusions

Patterns of SED and PA change from early to late childhood; with the exception of SED breaks and VPA, changes were detrimental. Total volumes and short bouts tended to track more strongly than longer bouts. Interventions to prevent declines in PA and increases in SED are important from early in life.
KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway
Authors: Zeng Fanchang , Luo Liumei , Li Daoyuan , Guo Juncheng , Guo Min
Published: March 2021

Background

Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa.

Methods

BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo.

Results

KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo.

Conclusion

Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.
TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway
Authors: Sun Tianshui , Bi Fangfang , Liu Zhuonan , Yang Qing
Published: March 2021

Background

Ovarian cancer (OV) is the deadliest gynecological cancer. Transmembrane protein 119 (TMEM119) has been reported as oncogene in several human cancers. However, the function of TMEM119 in OV is still poorly known.

Methods

Western blot and qRT-PCR were used to analyze TMEM119 levels. Transwell assays, wound healing assays, CCK-8 assays and EdU cell proliferation assays were designed to explore the function and potential mechanism of TMEM119 in malignant biological behaviors in OV.

Results

TMEM119 was observed to be overexpressed in OV tissues and associated with poor survival in OV patients. Knockdown and overexpression experiments demonstrated that TMEM119 promoted proliferation, invasion, and migration in OV cells in vitro. TMEM119 mRNA expression was related to the pathways of focal adhesion according to Gene Set Enrichment Analyses and was correlated with the mRNA expression level of platelet-derived growth factor receptor beta (PDGFRB). TMEM119 exerted oncogenic effects partially by regulating the expression of PDGFRB and by activating the PI3K/AKT signaling pathway.

Conclusions

Collectively, our findings highlight the potential role of TMEM119 in the malignant biological behavior of OV, which may serve as a potential biomarker and a therapeutic candidate for OV.
Psychosocial and economic impact of rheumatic diseases on caregivers of Mexican children
Authors: Fortuna-Reyna Brenda de Jesús , Peláez-Ballestas Ingris , García-Rodríguez Fernando , Faugier-Fuentes Enrique , Mendieta-Zerón Samara , Villarreal-Treviño Ana Victoria , Rosiles-De la Garza Sara Georgina , Reyes-Cordero Greta , Jiménez-Hernández Sol , Guadarrama-Orozco Jessica Haydee , de la O-Cavazos Manuel Enrique , Rubio-Pérez Nadina
Published: March 2021

Background

Pediatric rheumatic disease (PRD) patients and their caregivers face a number of challenges, including the consequences of the PRD in patients and the impact on multiple dimensions of the caregivers’ daily lives. The objective of this study is to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children.

Methods

This is a multicenter, cross-sectional study including primary caregivers of children and adolescents with PRD (JIA, JDM and JSLE) during April and November, 2019. A trained interviewer conducted the CAREGIVERS questionnaire, a specific, 28-item multidimensional tool validated to measure the impact on different dimensions of the lives of caregivers. Sociodemographic, clinical, and healthcare system data were collected for further analysis.

Results

Two hundred participants were recruited (women 169, 84.5%, aged 38 [IQR 33–44] years); 109 (54.5%) cared for patients with JIA, 28 (14%) JDM and 63 (31.5%) JSLE. The healthcare system was found to be determinant on the impact of the disease. The emotional impact was higher in all the participants, regardless of the specific diagnoses. The social dimension showed significant differences regarding PRD, healthcare system, time to reach the center, presence of disability, active disease, cutaneous and systemic manifestations, treatment and partner. Financial and work impacts were more frequent in those caring for JSLE and less so in those with a partner. Family relationships changed in 81 caregivers (25 [12.5%] worsened and 56 [28%] improved). No variables affecting spirituality were found. For caregivers without a partner, the social networks impact increased.

Conclusion

The influence of sociodemographic factors can be devastating on families with children with a PRD. These data will help physicians to identify the areas with the greatest need for intervention to achieve comprehensive care for caregivers and their patients.