bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic promoter system for well-controlled protein expression with different carbon sources in Saccharomyces cerevisiae
Authors: Deng Jiliang , Wu Yanling , Zheng Zhaohui , Chen Nanzhu , Luo Xiaozhou , Tang Hongting , Keasling Jay D. 
Published: October 2021

Abstract
Background
Saccharomyces cerevisiae is an important synthetic biology chassis for microbial production of valuable molecules. Promoter engineering has been frequently applied to generate more synthetic promoters with a variety of defined characteristics in order to achieve a well-regulated genetic network for high production efficiency. Galactose-inducible (GAL) expression systems, composed of GAL promoters and multiple GAL regulators, have been widely used for protein overexpression and pathway construction in S. cerevisiae. However, the function of each element in synthetic promoters and how they interact with GAL regulators are not well known.

Results
Here, a library of synthetic GAL promoters demonstrate that upstream activating sequences (UASs) and core promoters have a synergistic relationship that determines the performance of each promoter under different carbon sources. We found that the strengths of synthetic GAL promoters could be fine-tuned by manipulating the sequence, number, and substitution of UASs. Core promoter replacement generated synthetic promoters with a twofold strength improvement compared with the GAL1 promoter under multiple different carbon sources in a strain with GAL1 and GAL80 engineering. These results represent an expansion of the classic GAL expression system with an increased dynamic range and a good tolerance of different carbon sources.

Conclusions
In this study, the effect of each element on synthetic GAL promoters has been evaluated and a series of well-controlled synthetic promoters are constructed. By studying the interaction of synthetic promoters and GAL regulators, synthetic promoters with an increased dynamic range under different carbon sources are created.
Estimating the accumulative dose uncertainty for intracavitary and interstitial brachytherapy
Authors: Wang Binbing , Hu Weibiao , Shan Guoping , Xu Xiaoxian 
Published: October 2021

Abstract
Background
Image-guided adaptive brachytherapy shows the ability to deliver high doses to tumors while sparing normal tissues. However, interfraction dose delivery introduces uncertainties to high dose estimation, which relates to normal tissue toxicity. The purpose of this study was to investigate the high-dose regions of two applicator approaches in brachytherapy.

Method
For 32 cervical cancer patients, the CT images from each fraction were wrapped to a reference image, and the displacement vector field (DVF) was calculated with a hybrid intensity-based deformable registration algorithm. The fractional dose was then accumulated to calculate the position and the overlap of high dose (D2cc) during multiple fractions.

Result
The overall Dice similarity coefficient (DSC) of the deformation algorithm for the bladder and the rectum was (0.97 and 0.91). No significant difference was observed between the two applicators. However, the location of the intracavitary brachytherapy (ICBT) high-dose region was relatively concentrated. The overlap volume of bladder and rectum D2cc was 0.42 and 0.71, respectively, which was higher than that of interstitial brachytherapy (ISBT) (0.26 and 0.31). The cumulative dose was overestimated in ISBT cases when using the GEC-recommended method. The ratio of bladder and rectum D2cc to the GEC method was 0.99 and 1, respectively, which was higher than that of the ISBT method (0.96 and 0.94).

Conclusion
High-dose regions for brachytherapy based on different applicator types were different. The 3D-printed ICBT has better high-dose region consistency than freehand ISBT and hence is more predictable.
Redistributive effects of health care out-of-pocket payments in Cameroon
Authors: Ntembe Augustin , Tawah Regina , Faux Elkanah 
Published: October 2021

Abstract
Background
The bulk of health care financing in Cameroon is derived from out-of-pocket payments. Given that poverty is pervasive, with a third of the population living below the poverty line, health care financing from out-of-pocket payments is likely to have redistributive and equity effects. In addition, out-of-pocket payments on health care can limit the ability of households to afford non-healthcare goods and services.

Method
The study estimates the Kakwani index for analyzing tax progressivity and applies the model developed by Aronson, Johnson, and Lambert (1994) to measure the redistributive effects of health care financing using data from the 2014 Cameroon Household Survey. The estimated indexes measure the extent of the progressivity of health care payments and the reranking that results from the payments.

Results
The results indicate that out-of-pocket payments for health care in Cameroon in 2014 represented a significant share of household prepayment income. The results also show some evidence of inequity as few people change ranks after payment despite the slight progressivity of health care out-of-pocket payments.

Conclusion
The existence of some disparities among income groups implies that the burdens of ill-health and out-of-pocket payments are unequal. The detected disparities within income groups can be reduced by targeting low-income groups through increases in government expenditures on health care and pro-poor prioritization of the expenditures.
Laparoscopic nerve‑sparing radical hysterectomy for the treatment of cervical cancer: a meta-analysis of randomized controlled trials
Authors: Ma Linlin , Li Qiwei , Guo Ying , Tan Xiaoyu , Wang Mengying , Qi Qi 
Published: October 2021

Abstract
Background
The effects and safety of laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) in cervical cancer treatment remain unclear. This article aims to evaluate the role of LNSRH versus LRH in the treatment of cervical cancer. This is because the updated meta-analysis with synthesized data may provide more reliable evidence on the role of LNSRH and LRH.

Methods
We searched Pubmed et al. databases for randomized controlled trials (RCTs) involving laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) for cervical cancer treatment from the inception of databases to June 15, 2021. The RevMan 5.3 software was used for data analyses. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-9-0047/).

Results
Thirteen RCTs involving a total of 1002 cervical cancer patients were included. Synthesized results indicated that the duration of surgery of the LNSRH group was significantly longer than that of the LRH group [SMD 1.11, 95% CI (0.15 ~ 2.07), P = 0.02]. The time to intestinal function recovery [SMD −1.27, 95% CI (−1.84 ~ −0.69), P < 0.001] and the time to postoperative urinary catheter removal of the LNSRH group [SMD −1.24, 95% CI (−1.62 ~ −0.86), P < 0.001] were significantly less than that of the LRH group. There were no significant differences in the estimated blood loss [SMD 0.10, 95% CI (−0.14 ~ 0.34), P = 0.41], the length of parauterine tissue resection [SMD −0.10, 95% CI (−0.25 ~ 0.05), P = 0.19], length of vaginal excision [SMD 0.04, 95% CI (−0.26 ~ 0.34), P = 0.78], and incidence of intraoperative adverse events [RR 0.97, 95% CI (0.44 ~ 2.13), P = 0.94] between the LNSRH group and the LRH group.

Conclusions
LNSRH significantly results in earlier bladder and bowel function after surgery. Limited by sample size, LNSRH should be considered with caution in the future.
Food aversion during pregnancy and its association with nutritional status of pregnant women in Boricha Woreda, Sidama Regional State, Southern Ethiopia, 2019. A community based mixed crossectional study design
Authors: Yalew Abel , Tekle Silasie Wondwosen , Anato Anchamo , Fikrie Anteneh 
Published: October 2021

Abstract
Background
Despite high prevalence, food aversions are closely linked to the dietary intake of pregnant women. Thus, understanding this behavior is important in addressing the issue of maternal nutrition. Therefore, the aim of this study is to provide information on the prevalence and associated factors of food aversion and its relationship with the nutritional status of pregnant women in Boricha Woreda, Sidama Regional state, Southern Ethiopia, 2019.

Methods
A community based mixed cross sectional study was conducted among 505 randomly selected pregnant mothers at Boricha Woreda, Southern Ethiopia from June 1–20, 2019. Pre-tested and structured face-to-face interview questionnaire and focus group discussion guide were used to collect quantitative and qualitative data respectively. The quantitative data were cleaned, coded and entered into Epi Info version 7.1.4.0 and then exported to SPSS IBM version 20 for further analysis. The qualitative data were analyzed manually using a content analysis.The bi-variable and multivariable logistic regression was used to identify the possible factors of food aversion. AOR with the respective 95% CIs was used to declare statistical significance.

Results
Nearly, seven-in-ten (69.2%) of the pregnant women were averted of at least one food. Cereal (45.9%) and enset (44.2%) were averted by majority of the participants. The mean (± SD) MUAC measurement was 22.7 (± 2.4) cm. Pregnant women of age group of 24–28 [AOR = 3.04, 95% CI (1.72–5.35)] and 29–33 years [AOR = 2.00, 95% CI (1.02–3.92)], nausea during [AOR = 1.77, 95% CI (1.16–2.70)] and having additional meal [AOR = 1.68, 95% CI (1.02–2.75)] were significantly associated with food aversion. Maternal nutritional status and food aversion was sstatistically significant (p-value < 0.001).

Conclusion
High prevalence of food aversions (69.2%) and under nutrition (34.6%) among pregnant women is found. Therefore, the Woreda Health Office needs to intensify the integration of maternal nutrition into ANC services and training of health providers as well as critical appraisal of health extension workers should also be considered.
Functional assessment of stretch hyperreflexia in children with cerebral palsy using treadmill perturbations
Authors: Flux Eline , van der Krogt Marjolein M. , Harlaar Jaap , Buizer Annemieke I. , Sloot Lizeth H. 
Published: October 2021

Abstract
Background
As hyperactive muscle stretch reflexes hinder movement in patients with central nervous system disorders, they are a common target of treatment. To improve treatment evaluation, hyperactive reflexes should be assessed during activities as walking rather than passively. This study systematically explores the feasibility, reliability and validity of sudden treadmill perturbations to evoke and quantify calf muscle stretch reflexes during walking in children with neurological disorders.

Methods
We performed an observational cross-sectional study including 24 children with cerebral palsy (CP; 6–16 years) and 14 typically developing children (TD; 6–15 years). Short belt accelerations were applied at three different intensities while children walked at comfortable speed. Lower leg kinematics, musculo-tendon lengthening and velocity, muscle activity and spatiotemporal parameters were measured to analyze perturbation responses.

Results
We first demonstrated protocol feasibility: the protocol was completed by all but three children who ceased participation due to fatigue. All remaining children were able to maintain their gait pattern during perturbation trials without anticipatory adaptations in ankle kinematics, spatiotemporal parameters and muscle activity. Second, we showed the protocol’s reliability: there was no systematic change in muscle response over time (P = 0.21–0.54) and a bootstrapping procedure indicated sufficient number of perturbations, as the last perturbation repetition only reduced variability by ~ 2%. Third, we evaluated construct validity by showing that responses comply with neurophysiological criteria for stretch reflexes: perturbations superimposed calf muscle lengthening (P < 0.001 for both CP and TD) in all but one participant. This elicited increased calf muscle activity (359 ± 190% for CP and 231 ± 68% for TD, both P < 0.001) in the gastrocnemius medialis muscle, which increased with perturbation intensity (P < 0.001), according to the velocity-dependent nature of stretch reflexes. Finally, construct validity was shown from a clinical perspective: stretch reflexes were 1.7 times higher for CP than TD for the gastrocnemius medialis muscle (P = 0.017).

Conclusions
The feasibility and reliability of the protocol, as well as the construct validity—shown by the exaggerated velocity-dependent nature of the measured responses—strongly support the use of treadmill perturbations to quantify stretch hyperreflexia during gait. We therefore provided a framework which can be used to inform clinical decision making and treatment evaluation.
Feeding in the first six months of life is associated with the probability of having bronchiolitis: a cohort study in Spain
Authors: Gómez-Acebo Inés , Lechosa-Muñiz Carolina , Paz-Zulueta María , Sotos Trinidad Dierssen , Alonso-Molero Jéssica , Llorca Javier , Cabero-Perez María J. 
Published: October 2021

Abstract
Background
Breastfeeding is associated with lower incidence and severity of lower respiratory tract disease. However, little is known about the relationship between feeding type and breastfeeding duration with bronchiolitis in a child’s first year.

Methods
A prospective cohort study of 969 newborn babies were followed-up for 12 months to determine breastfeeding duration, feeding type, feeding trajectory, and bronchiolitis episodes at Marqués de Valdecilla University Hospital, Spain in 2018. Type of feeding was recorded by interviewing mothers at the time of hospital discharge and at 2, 4, 6, 9 and 12 months of life, in three categories: breastfeeding, mixed feeding and infant formula. Type of feeding at hospital discharge refers to feeding from birth to discharge. In any other times studied, it refers to feeding in the last 24 h. The association between the feeding type and bronchiolitis was analysed using logistic regression. Poisson regression was used to evaluate the association between feeding type and the number of bronchiolitis episodes with Kaplan-Meier estimators presenting the cumulative probability of suffering bronchiolitis. The results were adjusted for mother and child characteristics.

Results
Our data shows exclusive breastfeeding and mixed breastfeeding reduce the number of episodes of bronchiolitis. Regarding feeding at 4 months, exclusive breastfeeding reduced by 41% the number of episodes of bronchiolitis (adjusted incidence Ratio (aIR) 0.59, 95% CI 0.46, 0.76) and mixed feeding by 37% (aIR 0.63, 95% CI 0.47, 0.86). Moreover, changing from exclusive breastfeeding to mixed feeding increased the incidence of bronchiolitis compared with continuing exclusive breastfeeding. An early swap to mixed breastfeeding before months 2 or 4, was associated with a reduced the number of episodes of bronchiolitis, (aIR 0.53, 95% CI 0.39, 0.73 if introduction of mixed breastfeeding before month 2, and aIR 0.61, 95% CI 0.45, 0.83 if introduction of mixed breastfeeding before month 4), when compared with infant formula alone.

Conclusions
Any breastfeeding was associated with lower incidence of bronchiolitis and number of episodes of bronchiolitis in the first year of life. Consequently, promoting programmes facilitating exclusive or mixed breastfeeding would be a relevant measure in the prevention of bronchiolitis.
Overexpression of FGF2 delays the progression of osteonecrosis of the femoral head activating the PI3K/Akt signaling pathway
Authors: Lu Pei , Shen Yi-min , Hua Ting , Pan Ting , Chen Gang , Dai Teng , Shi Ke-qin 
Published: October 2021

Abstract
Background
The purpose of the current study was to explore the role and underlying mechanism of FGF-2 in dexamethasone (DEX)-induced apoptosis in MC3T3-E1 cells.

Methods
GSE21727 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. MC3T3-E1 cells were exposed to DEX at different concentrations (0, 10−8, 10−7, 10−6, 10−5 and 10−4 mol/L), and cell viability, flow cytometry and TUNEL assay were used to detect cell proliferation and apoptosis. An FGF-2-pcDNA3 plasmid (oe-FGF-2) was used to overexpress FGF-2, and western blotting was conducted to detect protein expression.

Results
We found that FGF-2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated FGF-2 gene and protein expression, inhibited viability and induced MC3T3-E1 cell apoptosis. Overexpression of FGF-2 reversed DEX-induced apoptosis in MC3T3-E1 cells. FGF-2-mediated anti-apoptosis was impaired by inactivating the PI3K/AKT pathway with LY294002. Moreover, overexpression of FGF2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model by regulation PI3K/Akt signaling pathway.

Conclusion
In conclusion, FGF-2 is effective at inhibiting DEX-induced MC3T3-E1 cell apoptosis through regulating PI3K/Akt signaling pathway.
Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis
Authors: Xie Guohui , Liang Chunhong , Yu Honglin , Zhang Qin 
Published: October 2021

Abstract
Background
Collagens are important structural components of intervertebral disc. A number of studies have been performed for association between polymorphisms of collagen genes and risk of intervertebral disc degeneration (IVDD) but yielded inconsistent results. Here, we performed a meta-analysis to investigate the association of collagen IX alpha 2 (COL9A2) Trp2, collagen IX alpha 3 (COL9A3) Trp3, collagen I alpha 1 (COL1A1) Sp1 and collagen XI alpha 1 (COL11A1) C4603T polymorphisms with susceptibility to IVDD.

Method
Eligible studies were retrieved by searching MEDLINE, EMBASE, Web of Science prior to 31 March, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for association strength.

Results
A total of 28 eligible studies (31 datasets comprising 5497 cases and 5335 controls) were included. COL9A2 Trp2 carriers had an increased risk of IVDD than non-carriers in overall population (OR = 1.43, 95% CI 0.99–2.06, P = 0.058), which did not reach statistical significance. However, Trp2 carriers had 2.62-fold (95% CI 1.15–6.01, P = 0.022) risk than non-carriers in Caucasians. COL9A3 Trp3 was not associated with IVDD risk (OR = 1.28, 95% CI 0.81–2.02, P = 0.299). T allele and TT genotype of COL1A1 Sp1 (+ 1245G > T) were correlated with increased risk of IVDD. Significant associations were found between COL11A1 C4603T and IVDD risk under allelic (OR = 1.33, 95% CI 1.20–1.48), dominant (OR = 1.45, 95% CI 1.26–1.67), recessive (OR = 1.55, 95% CI 1.21–1.98) and homozygote model (OR = 1.81, 95% CI 1.40–2.34).

Conclusions
COL1A1 Sp1 and COL11A1 C4603T polymorphism are associated with IVDD risk while the predictive roles of collagen IX gene Trp2/3 need verification in more large-scale studies.
Efficacy of a semirigid ankle brace in reducing mechanical ankle instability evaluated by 3D stress-MRI
Authors: Eberbach Helge , Gehring Dominic , Lange Thomas , Ovsepyan Spartak , Gollhofer Albert , Schmal Hagen , Wenning Markus 
Published: October 2021

Abstract
Background
Novel imaging technologies like 3D stress-MRI of the ankle allow a quantification of the mechanical instability contributing to chronic ankle instability. In the present study, we have tested the efficacy of a semirigid ankle brace on joint congruency in a plantarflexion/supination position with and without load.

Methods
In this controlled observational study of n = 25 patients suffering from mechanical ankle instability, a custom-built ankle arthrometer implementing a novel 3D-stress MRI technique was used to evaluate the stabilizing effect of an ankle brace. Three parameters of joint congruency (i.e., 3D cartilage contact area fibulotalar, tibiotalar horizontal and tibiotalar vertical) were measured. The loss of cartilage contact area from neutral position to a position combined of 40° of plantarflexion and 30° of supination without and with axial load of 200 N was calculated. A semirigid ankle brace was applied in plantarflexion/supination to evaluate its effect on joint congruence. Furthermore, the perceived stability of the brace during a hopping task was analyzed using visual analogue scale (VAS).

Results
The application of a semirigid brace led to an increase in cartilage contact area (CCA) when the foot was placed in plantarflexion and supination. This effect was visible for all three compartments of the upper ankle joint (P < 0.001; η2 = 0.54). The effect of axial loading did not result in significant differences. The subjective stability provided by the brace (VAS 7.6/10) did not correlate to the magnitude of the improvement of the overall joint congruency.

Conclusions
The stabilizing effect of the semirigid ankle brace can be verified using 3D stress-MRI. Providing better joint congruency with an ankle brace may reduce peak loads at certain areas of the talus, which possibly cause osteochondral or degenerative lesions. However, the perceived stability provided by the brace does not seem to reflect into the mechanical effect of the brace.
Trial registration The study protocol was prospectively registered at the German Clinical Trials Register (#DRKS00016356).