bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placebo design in WHO-registered trials of Chinese herbal medicine need improvements
Authors: Zhang Xuan , Tian Ran , Zhao Chen , Tang Xudong , Lu Aiping , Bian Zhaoxiang 
Published: November 2019

Abstract

Background
Physical identical and pharmacological inert are the basic requirements for placebo design, which are essential in clinical trials to evaluate the efficacy of an intervention. However, it is difficult to makeup a placebo of Chinese herbal medicine (CHM) because of special color, taste and smell, etc. Currently, there is no specific requirements and standards for the creation of a CHM-placebo. The purpose of this study is to review the characteristics of the CHM-placebo design and application in registered clinical trials with CHM interventions and identify the common problems, if any.

Methods
The World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) was systematically searched for CHM interventional trials with placebo-controlled design up to 31 December 2017. Registered information of each included trial was collected from specific registries involved in ICTRP through hyperlinks. Descriptive statistics were used to analyze the characteristics of placebo design in CHM trial registrations.

Results
A total of 889 CHM interventional trials were registered from 1999 to 2017, and 40.8% (363) of them included CHM-placebo control design. The common ways of their design were: placebo as sole control (191, 52.6%); placebo as add-on control with baseline treatment (84, 23.1%); and placebo as double-dummy control (57, 15.7%). Among 363 included trials, 46 (12.7%) reported the compositions of placebos, including CHM ingredients (17 trials), excipients and other agents (29 trials). 2 (0.6%) reported pharmacological inert testing, and 52 (14.3%) descripted their placebos to be physically identical with the CHMs. 14 (3.9%) reported quality control of placebos, and 2 (0.6%) provided blinding assessment of placebos.

Conclusions
The placebos included in most CHM trial registrations is not optimal in terms of placebo design, application, evaluation and reporting. Specific guidelines or standards of CHM-placebo design, including usage requirements, preparation specifications, quality assessments and reporting guidelines should be developed thus to improve their quality.
Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma
Authors: Shademan Milad , Naseri Salanghuch Azam , Zare Khadijeh , Zahedi Morteza , Foroughi Mohammad Ali , Akhavan Rezayat Kambiz , Mosannen Mozaffari Hooman , Ghaffarzadegan Kamran , Goshayeshi Ladan , Dehghani Hesam 
Published: November 2019

Abstract

Background
Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas.

Methods
In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense–antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes.

Results
PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated.

Conclusions
We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes.
Omega-3 polyunsaturated fatty acids status and cognitive function in young women
Authors: Cook Rebecca L. , Parker Helen M. , Donges Cheyne E. , O’Dwyer Nicholas J. , Cheng Hoi Lun , Steinbeck Katharine S. , Cox Eka P. , Franklin Janet L. , Garg Manohar L. , O’Connor Helen T. 
Published: November 2019

Abstract

Background
Research indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women.

Methods
This was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18–35 y) of normal weight (NW: BMI 18.5–24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 < 5.47%, T2 = 5.47–6.75%, T3 > 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA.

Results
Two hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15–0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09–0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004).

Conclusions
Cognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted.
Do socio-demographic characteristics and/or health status explain the magnitude of differences between patient and general public utility values? A chronic low back pain patients case study
Authors: van Dongen J. M. , van Hooff M. L. , Finch A. P. , van Tulder M. W. , Bosmans J. E. , Ostelo R. W. J. G. , de Kleuver M. 
Published: November 2019

Abstract

Background
Utility values can be obtained from different respondent groups, including patients and members of the general public. Evidence suggests that patient values are typically higher than general public values. This study explores whether the magnitude of disagreement between both values can be explained by socio-demographic characteristics and/or health status.

Methods
Data of 5037 chronic low back pain patients were used. Self-reported EQ-VAS was employed as a proxy of patients’ preference for their own health state. General public values for the patients’ EQ-5D-3L health states were obtained using the Dutch VAS-based tariff. The difference between patient and general public values was assessed using a paired t-test. Subsequently, this difference was used as a dependent variable and regressed upon dummy variables of socio-demographic and health status characteristics. Coefficients represented age, gender, education level, social support, back pain intensity, leg pain intensity, functional status, comorbidities, catastrophizing, and treatment expectations.

Results
Patient values were higher than general public values (0.069; 95%CI:0.063–0.076). The magnitude of disagreement between both values was associated with age, gender, education level, social support, functional status, and comorbidities, but not with back pain intensity, leg pain intensity, catastrophizing, and treatment expectations.

Conclusions
Patients were found to value their own health status higher than members of the general public. The magnitude of disagreement between both values was found to differ by various socio-demographic and/or health status characteristics. This suggest that patient characteristics account for a relevant fraction of the identified disagreements between patient and general public values, and that mechanisms thought to be responsible for these disagreements, such as adaptation and response shift, have a differential impact across patient sub-groups.
Trends in peritoneal surface malignancies: evidence from a Czech nationwide population-based study
Authors: Klos Dušan , Riško Juraj , Loveček Martin , Skalický Pavel , Svobodová Ivana , Krejčí Denisa , Melichar Bohuslav , Mohelníková-Duchoňová Beatrice , Lemstrová Radmila 
Published: November 2019

Abstract

Background
The aim of this study is to identify the incidence trends of primary and secondary peritoneal surface malignancies in a representative Czech population.

Methods
Data were obtained from patients registered in the Czech National Cancer Registry between 1979 and 2016. The incidence rates were analyzed between 2012 and 2016. To observe the incidence trends, we analyzed the data from two time periods, 1979–2005 and 2006–2016. The analyzed data included age, sex, and the histological types and primary origins of the malignancies. The Cochrane-Armitage test for linear trends was used for verification of the null hypothesis. The significance level established for hypothesis testing was p = 0.05.

Results
Between 2012 and 2016, 230 patients with primary peritoneal tumors were identified and divided into the following groups according to their “International Statistical Classification of Diseases and Related Health Problems, 10th revision” codes: malignant neoplasm of specified parts of the peritoneum (C48.1); malignant neoplasm of the peritoneum, unspecified (C48.2); and malignant neoplasm of overlapping sites of the retroperitoneum and peritoneum (C48.8). Moreover, 549 primary tumors of the appendix (C18.1, encompassing all appendiceal malignancies) and 3137 secondary synchronous peritoneal carcinomatoses of other primary origins were documented. The age-adjusted incidence of primary peritoneal tumors in 2012–2016 was 4.36/year/1,000,000 inhabitants. The age-adjusted incidence of synchronous secondary peritoneal malignancies in 2014–2016 was 99.0/year/1,000,000 inhabitants. The diagnoses of primary peritoneal malignancies followed a stable trend between 1979 and 2016. However, the incidences of primary tumors of the appendix increased by 76.7%.

Conclusions
The data produced in our study ought to clarify the status of peritoneal surface malignancies in the Czech Republic, which can lead to improved planning and development of therapeutic interventions as well as physician training.
GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients
Authors: Neckmann Ulrike , Wolowczyk Camilla , Hall Martina , Almaas Eivind , Ren Jiang , Zhao Sen , Johannessen Bjarne , Skotheim Rolf I. , Bjørkøy Geir , ten Dijke Peter , Holien Toril 
Published: November 2019

Abstract
Background
In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood.

Methods
We analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis. CRISPR/Cas9 gene editing was used for mechanistic studies in the same cell lines. Furthermore, we analyzed gene expression patterns in human breast cancer biopsies obtained from public datasets to evaluate co-expression and possible relations to clinical outcome.

Results
We found that mRNA levels of the BMP-antagonist Grem1, encoding gremlin1, and the ligand Bmp4 were both significantly upregulated in cells and primary tumors of 66cl4 compared to 67NR. Depletion of gremlin1 in 66cl4 could impair metastasis to the lungs in this model. Furthermore, we found that expression of Grem1 correlated with upregulation of several stem cell markers in 66cl4 cells compared to 67NR cells. Both in the mouse model and in patients, expression of GREM1 associated with extracellular matrix organization, and formation, biosynthesis and modification of collagen. Importantly, high expression of GREM1 predicted poor prognosis in estrogen receptor negative breast cancer patients. Analyses of large patient cohorts revealed that amplification of genes encoding BMP-antagonists and elevation of the corresponding transcripts is evident in biopsies from more than half of the patients and much more frequent for the secreted BMP-antagonists than the intracellular inhibitors of SMAD signaling.

Conclusion
In conclusion, our results show that GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients. Gremlin1 could represent a novel target for therapy.
Pain, functional disability, and their Association in Juvenile Fibromyalgia Compared to other pediatric rheumatic diseases
Authors:   for the CARRA Registry Investigators, Connelly Mark , Weiss Jennifer E. 
Published: November 2019

Abstract

Background
Severe pain and impairments in functioning are commonly reported for youth with juvenile fibromyalgia. The prevalence and impact of pain in other diseases commonly managed in pediatric rheumatology comparatively have been rarely systematically studied. The objective of the current study was to determine the extent to which high levels of pain and functional limitations, and the strength of their association, are unique to youth with juvenile primary fibromyalgia syndrome/JPFS) relative to other pediatric rheumatic diseases.

Methods
Using data from 7753 patients enrolled in the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry, we compared the levels and association of pain and functional limitations between youth with JPFS and those with other rheumatic diseases.

Results
Pain levels were rated highest among youth with JPFS (M = 6.4/10, SD = 2.4) and lowest for juvenile dermatomyositis (M = 1.7/10, SD = 2.2), with pain significantly higher in the JPFS group than any other pediatric rheumatic disease (effect sizes = .22 to 1.05). Ratings on measures of functioning and well-being also were significantly worse for patients with JPFS than patients with any other rheumatic disease (effect sizes = .62 to 1.06). The magnitude of association between pain intensity and functional disability, however, generally was higher in other rheumatic diseases than in JPFS. Pain was most strongly associated with functional limitations in juvenile dermatomyositis, juvenile idiopathic arthritis, and mixed connective tissue disease.

Conclusions
JPFS is unique among conditions seen in pediatric rheumatology with regard to ratings of pain and disability. However, pain appears to be comparably or more highly associated with level of functional impairment in other pediatric rheumatic diseases. Pain in childhood rheumatic disease thus would benefit from increased prioritization for research and treatment.
Modular motor control of the sound limb in gait of people with trans-femoral amputation
Authors: De Marchis Cristiano , Ranaldi Simone , Serrao Mariano , Ranavolo Alberto , Draicchio Francesco , Lacquaniti Francesco , Conforto Silvia 
Published: November 2019

Abstract

Background
The above-knee amputation of a lower limb is a severe impairment that affects significantly the ability to walk; considering this, a complex adaptation strategy at the neuromuscular level is needed in order to be able to move safely with a prosthetic knee. In literature, it has been demonstrated that muscle activity during walking can be described via the activation of a small set of muscle synergies. The analysis of the composition and the time activation profiles of such synergies have been found to be a valid tool for the description of the motor control schemes in pathological subjects.

Methods
In this study, we used muscle synergy analysis techniques to characterize the differences in the modular motor control schemes between a population of 14 people with trans-femoral amputation and 12 healthy subjects walking at two different (slow and normal self-selected) speeds. Muscle synergies were extracted from a 12 lower-limb muscles sEMG recording via non-negative matrix factorization. Equivalence of the synergy vectors was quantified by a cross-validation procedure, while differences in terms of time activation coefficients were evaluated through the analysis of the activity in the different gait sub-phases.

Results
Four synergies were able to reconstruct the muscle activity in all subjects. The spatial component of the synergy vectors did not change in all the analysed populations, while differences were present in the activity during the sound limb’s stance phase. Main features of people with trans-femoral amputation’s muscle synergy recruitment are a prolonged activation of the module composed of calf muscles and an additional activity of the hamstrings’ module before and after the prosthetic heel strike.

Conclusions
Synergy-based results highlight how, although the complexity and the spatial organization of motor control schemes are the same found in healthy subjects, substantial differences are present in the synergies’ recruitment of people with trans femoral amputation. In particular, the most critical task during the gait cycle is the weight transfer from the sound limb to the prosthetic one. Future studies will integrate these results with the dynamics of movement, aiming to a complete neuro-mechanical characterization of people with trans-femoral amputation’s walking strategies that can be used to improve the rehabilitation therapies.
Determinants of nutritional status among children under age 5 in Ethiopia: further analysis of the 2016 Ethiopia demographic and health survey
Authors: Amare Zerihun Yohannes , Ahmed Mossa Endris , Mehari Adey Belete 
Published: November 2019

Abstract

Background
The aim of this study was to examine the determinants of nutritional status among children under age 5 (0–59 months) in Ethiopia. Child malnutrition is an underlying cause of almost half (45%) of child deaths, particularly in low socioeconomic communities of developing countries. In Ethiopia, the prevalence of stunting decreased from 47% in 2005 to 39% in 2016, but the prevalence of wasting changed little over the same time period (from 11 to 10%). Despite improvements in reducing the prevalence of malnutrition, the current rate of progress is not fast enough to reach the World Health Organization global target for reducing malnutrition 40% by 2025.

Methods
This study used data from the 2016 Ethiopia Demographic and Heath Survey (EDHS). The analysis used stunting and wasting as dependent variables, while the independent variables were characteristics of children, mothers, and households. Logistic regression was used to analyze the determinants of nutritional status among children. Bivariate analysis was also used to analyze the association between the dependent and independent variables.

Results
Study results show that child’s age, sex, and perceived birth weight, mother’s educational status, body mass index (BMI), and maternal stature, region, wealth quintile, type of toilet facility, and type of cooking fuel had significant associations with stunting. Child’s age, sex, and perceived birth weight, mother’s BMI, and residence and region showed significant associations with wasting. The study found that child, maternal, and household characteristics were significantly associated with stunting and wasting among children under age 5.

Conclusion
These findings imply that a multi-sectorial and multidimensional approach is important to address malnutrition in Ethiopia. The education sector should promote reduction of cultural and gender barriers that contribute to childhood malnutrition. The health sector should encourage positive behaviors toward childcare and infant feeding practices. More should be done to help households adopt improved types of toilet facilities and modern types of cooking fuels.