bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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.
Fishers and groupers (Epinephelus marginatus and E. morio) in the coast of Brazil: integrating information for conservation
Authors: Begossi Alpina , Salyvonchyk Svetlana , Glamuzina Branko , de Souza Shirley Pacheco , Lopes Priscila F. M. , Priolli Regina H. G. , do Prado Djalma Osmanir , Ramires Milena , Clauzet Mariana , Zapelini Cleverson , Schneider Daiana T. , Silva Luis T. , Silvano Renato A. M.
Published: November 2019

Background

Groupers are a vulnerable but economically important group of fish, especially for small-scale fisheries. We investigated catches and local ecological knowledge (LEK) of diet, habitat, and past fishing experiences.

Methods

Landings, prices, interviews, and restaurants demand for two species,Epinephelus marginatus(dusky grouper) andEpinephelus morio(red grouper), were registered.

Results

We visited 74 markets and 79 sites on the coast of Brazil in 2017–2018, and we interviewed 71 fishers: Bahia (NE), Rio de Janeiro and São Paulo (SE), and Santa Catarina (S). The landings sampled of dusky grouper (2016–2017) in Rio de Janeiro were:n = 222, size 38–109 cm, weight 1–24 kg, average 3.84 kg; in São Paulo, São Sebastião were:n = 47, size 39–106 cm, weight 2–8 kg, average of 2.77 kg; and at Santos:n = 80, 26–120 cm, weight 0.36–15 kg, average 2.72 kg. Red grouper was observed in markets in the northeastern Brazil. We did not observeEpinephelus marginatusfrom Bahia northward; a maximum size of 200 cm was reported south of the Bahia, besides Rio de Janeiro and São Paulo coasts, 20 years ago (or longer) by 12 fishers. Local knowledge of fishers was important for grouper data of habitat and diet; the reproduction period was identified by fishers as September to March.

Conclusions

Groupers can be considered as a cultural and ecological keystone species. We suggest protective measures: 1) fishing zoning, 2) islands (MPAs) with the surveillance of fishers, 3) late Spring and early Summer as key periods for management (grouper reproduction), 4) studies on grouper larvae, 5) mapping of fishing spots, 6) studies on local knowledge. Collaboration with small-scale fishers and local knowledge could contribute to low-conflict management measures. In that regard, integrative models of management from Latin America, by using local knowledge and citizen science, could produce successful grouper management for Brazilian data-poor fisheries, a contrasting reality to the Mediterranean areas. Finally, the distribution ofE. marginatusin Brazil leave us with questions: a) Have dusky groupers disappeared from Bahia because of a decline in the population? b) Was it uncommon in Northeast Brazil? c) Did changes in water temperatures forced a movement southward?
Readiness to change among involuntarily and voluntarily admitted patients with substance use disorders
Authors: Opsal Anne , Kristensen Øistein , Clausen Thomas
Published: November 2019

Background

Health care workers in the addiction field have long emphasised the importance of a patient’s motivation on the outcome of treatments for substance use disorders (SUDs). Many patients entering treatment are not yet ready to make the changes required for recovery and are often unprepared or sometimes unwilling to modify their behaviour. The present study compared stages of readiness to change and readiness to seek help among patients with SUDs involuntarily and voluntarily admitted to treatment to investigate whether changes in the stages of readiness at admission predict drug control outcomes at follow-up.

Methods

This prospective study included 65 involuntarily and 137 voluntarily admitted patients treated in three addiction centres in Southern Norway. Patients were evaluated using the Europ-ASI, Readiness to Change Questionnaire (RTCQ), and Treatment Readiness Tool (TReaT).

Results

The involuntarily admitted patients had significantly lower levels of motivation to change than the voluntarily admitted patients at the time of admission (39% vs. 59%). The majority of both involuntarily and voluntarily admitted patients were in the highest stage (preparation) for readiness to seek help at admission and continued to be in this stage at discharge. The stage of readiness to change at admission did not predict abstinence at follow-up. The only significant predictor of ongoing drug use at 6 months was SUD severity at baseline.

Conclusions

The majority of involuntarily admitted patients scored high on motivation to seek help. Their motivation was stable at a fairly high level during their stay, and even improved in some patients. Thus, they were approaching the motivation stage similar to the voluntarily admitted patients at the end of hospitalization. Therapists should focus on both motivating patients in treatment and adapting the treatment according to SUD severity.

Trial registration

ClinicalTrials.gov, NCT00970372. Registered 1 September 2008,https://clinicaltrials.gov/ct2/show/NCT00970372. The trial was registered before the first participant was enrolled. The fist participant was enrolled September 02, 2009.
Association between Epstein-Barr virus and Thymic epithelial tumors: a systematic review
Authors: Zhang Guofei , Yu Zipu , Shen Gang , Chai Ying , Liang Chengxiao
Published: November 2019

The possible role of Epstein-Barr virus (EBV) in the pathogenesis of thymic epithelial tumors (TET) remains controversial. This study aimed to determine the prevalence of EBV in TET. We conducted a systematic review of relevant English-language studies published between January 1980 and December 2013. Effect size was calculated as event rates (95% confidence interval [CI]) by homogeneity testing using Cochran’s Q and I2 statistics for benign TET, benign TET with myasthenia gravis (MG), and thymic carcinoma (TC). Among 136 potentially relevant studies, 22 met the inclusion criteria. Despite a considerable degree of heterogeneity, the pooled estimated incidences were 9% (95% CI, 1–23%), 20% (95% CI, 0–54%), and 6% (95% CI, 0–21%) for benign TET, benign TET with MG, and TC, respectively. There was significant heterogeneity among studies that used in situ hybridization (ISH) for both benign TET and benign TET with MG. According to the random-effects model, studies employing ISH yielded lower point estimates of EBV prevalence (5%) than those employing other methods (33%). Using the random-effects model, we found a lack of significant heterogeneity among studies from different geographic regions (p = 0.0848). Further, 12 of 23 lymphoepithelioma-like carcinoma (LELC) cases tested EBV-positive. The prevalence of EBV in benign TET with or without MG was lower than in nasopharyngeal carcinoma, suggesting that EBV plays a minor role in TET pathogenesis. Although the prevalence of EBV in TC was also low, EBV may play an important causal role in LELC. Further research is needed to clarify these associations.
Prenatal diagnosis of 4953 pregnant women with indications for genetic amniocentesis in Northeast China
Authors: Dai Rulin , Yu Yang , Xi Qi , Hu Xiaonan , Zhu Haibo , Liu Ruizhi , Wang Ruixue
Published: November 2019

Background

Several different technologies are used for prenatal screening procedures and genetic diagnostic technologies. We aimed to investigate the rates of chromosomal abnormalities in cases with different abnormal prenatal indications and to determine the relationships between fetal chromosomal abnormalities and indicators of prenatal abnormalities in Northeast China.

Methods

We evaluated 4953 16- to 23-week singleton gestation cases using amniocentesis and a total of 3583 participants received serological screening. Fetal chromosomal analyses were performed for all samples using fluorescence in situ hybridization and karyotyping.

Results

Among these samples, 204 (4.12%) had fetal chromosomal abnormalities. A total of 3583 participants received serological screening, among whom 102 (2.85%) exhibited positive results. A total of 309 participants had ultrasonography; 42 (13.6%) of these had abnormalities. Among 97 participants who had non-invasive prenatal testing (NIPT), 59 (61%) had positive results. Among 1265 participants with advanced maternal age, 78 (6.2%) had abnormal results.

Conclusion

The serological screening and NIPT that were included in the prenatal screening methods all had false positive and false negative rates. Although they are both prenatal screening techniques, maternal serum screening cannot be replaced by NIPT. The pregnancy women should accept NIPT in a qualified prenatal diagnostic center. We recommend that pregnant women at high or critical risk undergoing prenatal screening should confirm the fetal karyotype through amniocentesis. Moreover, if women receive a positive result via NIPT, they should not have a pregnancy termination without undergoing further prenatal diagnosis.
Effect of tranexamic acid on mortality in patients with haemoptysis: a nationwide study
Authors: Kinoshita Takahiro , Ohbe Hiroyuki , Matsui Hiroki , Fushimi Kiyohide , Ogura Hiroshi , Yasunaga Hideo
Published: November 2019

Background

Although tranexamic acid is widely used in patients with haemoptysis, whether it improves mortality has not been well investigated. The aim of this study was to evaluate the effect of tranexamic acid on in-hospital mortality among patients with haemoptysis.

Methods

This was a retrospective study using data from the Japanese Diagnosis Procedure Combination inpatient database. We identified all cases of emergency admission due to haemoptysis from July 2010 to March 2017. Patients were divided into two groups: a control group, and a tranexamic acid group (those who received tranexamic acid on the day of admission). The primary outcome was in-hospital mortality, with secondary outcomes of hospital stay length and total healthcare cost. The data were evaluated using a propensity score matching analysis.

Results

Among 28,539 included patients, 17,049 patients received tranexamic acid and 11,490 patients did not. Propensity score analysis generated 9933 matched pairs. Compared to the control group, patients in the tranexamic acid group had significantly lower in-hospital mortality (11.5% vs. 9.0%; risk difference, − 2.5%; 95% confidence interval (CI), − 3.5 to − 1.6%), shorter hospital stays (18 ± 24 days vs. 16 ± 18 days; risk difference, − 2.4 days; 95% CI, − 3.1 to − 1.8 days), and lower total healthcare costs ($7573 ± 10,085 vs. $6757 ± 9127; risk difference, $− 816; 95% CI, $− 1109 to − 523).

Conclusions

Tranexamic acid may reduce in-hospital mortality among patients with haemoptysis requiring emergency admission.
Low-flow assessment of current ECMO/ECCO2R rotary blood pumps and the potential effect on hemocompatibility
Authors: Gross-Hardt Sascha , Hesselmann Felix , Arens Jutta , Steinseifer Ulrich , Vercaemst Leen , Windisch Wolfram , Brodie Daniel , Karagiannidis Christian
Published: November 2019

Background

Extracorporeal carbon dioxide removal (ECCO2R) uses an extracorporeal circuit to directly remove carbon dioxide from the blood either in lieu of mechanical ventilation or in combination with it. While the potential benefits of the technology are leading to increasing use, there are very real risks associated with it. Several studies demonstrated major bleeding and clotting complications, often associated with hemolysis and poorer outcomes in patients receiving ECCO2R. A better understanding of the risks originating specifically from the rotary blood pump component of the circuit is urgently needed.

Methods

High-resolution computational fluid dynamics was used to calculate the hemodynamics and hemocompatibility of three current rotary blood pumps for various pump flow rates.

Results

The hydraulic efficiency dramatically decreases to 5–10% if operating at blood flow rates below 1 L/min, the pump internal flow recirculation rate increases 6–12-fold in these flow ranges, and adverse effects are increased due to multiple exposures to high shear stress. The deleterious consequences include a steep increase in hemolysis and destruction of platelets.

Conclusions

The role of blood pumps in contributing to adverse effects at the lower blood flow rates used during ECCO2R is shown here to be significant. Current rotary blood pumps should be used with caution if operated at blood flow rates below 2 L/min, because of significant and high recirculation, shear stress, and hemolysis. There is a clear and urgent need to design dedicated blood pumps which are optimized for blood flow rates in the range of 0.5–1.5 L/min.
Recruitment effort and costs from a multi-center randomized controlled trial for treating depression in type 2 diabetes
Authors: Myers Barbara A. , Pillay Yegan , Guyton Hornsby W. , Shubrook Jay , Saha Chandan , Mather Kieren J. , Fitzpatrick Karen , de Groot Mary
Published: November 2019

Background

Participant recruitment for clinical trials is a significant challenge for the scientific research community. Federal funding agencies have made continuation of funding of clinical trials contingent on meeting recruitment targets. It is incumbent on investigators to carefully set study recruitment timelines and resource needs to meet those goals as required under current funding mechanisms. This paper highlights the cost, labor, and barriers to recruitment for Program ACTVE II, a successful multisite randomized controlled trial of behavioral treatments for depression in adults with type 2 diabetes, conducted in rural and urban settings in three states.

Methods

Quantitative and qualitative data on recruitment were gathered from study staff throughout the study recruitment period and were used to calculate costs and effort. The study utilized two main approaches to recruitment: (1) relying on potential participants to see ads in the community and call a toll-free number; and (2) direct phone calls to potential participants by study staff.

Results

Contact was attempted with 18,925 people to obtain the enrolled sample of 140. The cost of recruitment activities during the 4.5-year recruitment period totaled $190,056, an average cost of $1358 per enrolled participant. Qualitative evaluations identified multiple barriers to recruitment.

Conclusions

Recruitment for Program ACTIVE II exemplifies the magnitude of resources needed to reach recruitment targets in the current era. Continuous evaluation, flexibility, and adaptation are required on the part of investigators, community partners, and funding agencies to successfully reach high-risk populations in rural and urban areas.

Trial registration

ClinicalTrials.gov, NCT03371940. Registered on 13 December 2017.
Early rheumatoid arthritis is characterised by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin
Authors: Raza K.
Published: November 2019

A study by Raza et al., published in this journal in 2005, identified that RA patients, within 3 months of symptom onset, had a synovial fluid cytokine profile that was distinct from that of patients with other inflammatory arthritides of similarly short duration. This profile, which was transient, was characterised by cytokines of stromal and T cell origin. These findings suggested that the first few months after symptom onset were associated with changes in the early RA joint that differed from those operating at later stages. The significance of this paper’s methodological approach and its findings, and how they relate to subsequent literature, are discussed.
Under nutrition as a predictor of poor academic performance; the case of Nekemte primary schools students, Western Ethiopia
Authors: Seyoum Dejene , Tsegaye Reta , Tesfaye Amanuel
Published: November 2019

Objective

Though gradual improvements are exist; Ethiopia’s learning outcomes are still low in primary schools. Academic achievement of school age children can be affected by several factors such as nutritional status, socio-economic and demographic factors. The aim of this study was to assess predictors of poor academic performance in Nekemte Primary school students, Western Ethiopia.

Results

A total of 362 schoolchildren and their parents were involved in the study. The study involved interviewing the participants and their parents, anthropometric measurement of participants and their document review. The prevalence of stunting and underweight was 30.2% and 45.9% respectively. Of the total study participants, 32.2% of them were poor in academic achievement. Variables like Being underweight (Adjusted odds ratio (AOR): 0.57; 95% Confidence interval (CI) 0.23–0.82), Skipping breakfast (AOR: 2.1; 95% CI 1.42–5.76), stunting (AOR: 0.66; 95% CI 0.12–0.93), being male (AOR: 2.8; 95% CI 1.79–4.52), participants whom mothers didn’t attend formal education (AOR: 0.62; 95% CI 0.37–0.92) were significantly associated with academic performance. Thus, Modifiable factors like under nutrition should be a great concern to improve the overall achievement of children in schooling.
Eliciting dose is associated with tolerance development in peanut and cow’s milk allergic children
Authors: Nitsche C. , Westerlaken-van Ginkel C. D. , Kollen B. J. , Sprikkelman A. B. , Koppelman G. H. , Dubois A. E. J.
Published: November 2019

Background

Tolerance development rates differ between food allergies. Almost all previous studies have not used the gold standard method, the double-blind, placebo-controlled food challenge (DBPCFC), which may affect the reported prevalence rates. Little is known about the association of the eliciting dose (ED) obtained during the initial DBPCFC with later tolerance development.

Methods

This was a retrospective, tertiary care study of children who had a positive DBPCFC to either peanut, milk or egg, and at least one follow-up food challenge (open or DBPCFC) with the same food. The association between ED and negative (tolerant) follow-up food challenge outcome was analyzed by logistic regression, with adjustment for confounders. Suspected confounders were initial DBPCFC test characteristics, atopic comorbidities and serum specific IgE (sIgE) levels.

Results

In 47 peanut allergic children, tolerance developed in 27.7% (median follow-up duration of 43 months). In 80 milk (follow-up 23 months) and 55 egg (follow-up 37 months) allergic children, tolerance developed in 55.0% and 65.5%. The ED obtained during the initial DBPCFC was significantly associated with tolerance development in peanut and milk allergy, but not in egg allergy.

Conclusion

Approximately 1 out of 4 children with DBPCFC confirmed peanut allergy developed tolerance, compared to more than half of the children with milk or egg allergy, respectively. Tolerance development in peanut and milk allergy is significantly associated with ED at initial DBPCFC.
Ultra-short-term wind speed forecasting based on support vector machine with combined kernel function and similar data
Authors: He Jian , Xu Jingle
Published: November 2019

The accuracy of wind power prediction is very important for the stable operation of a power system. Ultra-short-term wind speed forecasting is an effective way to ensure real-time and accurate wind power prediction. In this paper, a short-term wind speed forecasting method based on a support vector machine with a combined kernel function and similar data is proposed. Similar training data are selected based on the wind tendency, and a combination of two kinds of kernel functions is applied in forecasting using a support vector machine. The forecasting results for a wind farm in Ningxia Province indicate that a combination of kernel functions with complementary advantages outperforms each single function, and forecasting models based on grouped wind data with a similar tendency could reduce the forecasting error. Furthermore, more accurate wind forecasting results ensure better wind power prediction.
Quantifying the contribution of microbial immigration in engineered water systems
Authors: Mei Ran , Liu Wen-Tso
Published: November 2019

Immigration is a process that can influence the assembly of microbial communities in natural and engineered environments. However, it remains challenging to quantitatively evaluate the contribution of this process to the microbial diversity and function in the receiving ecosystems. Currently used methods, i.e., counting shared microbial species, microbial source tracking, and neutral community model, rely on abundance profile to reveal the extent of overlapping between the upstream and downstream communities. Thus, they cannot suggest the quantitative contribution of immigrants to the downstream community function because activities of individual immigrants are not considered after entering the receiving environment. This limitation can be overcome by using an approach that couples a mass balance model with high-throughput DNA sequencing, i.e., ecogenomics-based mass balance. It calculates the net growth rate of individual microbial immigrants and partitions the entire community into active populations that contribute to the community function and inactive ones that carry minimal function. Linking activities of immigrants to their abundance further provides quantification of the contribution from an upstream environment to the downstream community. Considering only active populations can improve the accuracy of identifying key environmental parameters dictating process performance using methods such as machine learning.
Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer
Authors: Wierstra Peter , Sandker Gerwin , Aarntzen Erik , Gotthardt Martin , Adema Gosse , Bussink Johan , Raavé René , Heskamp Sandra
Published: November 2019

Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient stratification is based on immunotherapy marker expression through immunohistochemical analysis on biopsied material. However, expression can be heterogeneous within and between tumor lesions, amplifying the sampling limitations of biopsies. Analysis of immunotherapy target expression by non-invasive quantitative molecular imaging with PET or SPECT may overcome this issue. In this review, an overview of tracers that have been developed for preclinical and clinical imaging of key immunotherapy targets, such as programmed cell death-1, programmed cell death ligand-1, IDO1 and cytotoxic T lymphocyte-associated antigen-4 is presented. We discuss important aspects to consider when developing such tracers and outline the future perspectives of molecular imaging of immunotherapy markers.

Graphical abstract

Current techniques in immune checkpoint imaging and its potential for future applications
Negotiating Lay and Clinical Issues: Implementing a Lay Navigation Program in Cancer Care
Authors: Holdsworth Laura M. , Zionts Dani , Wang Suwei , Veruttipong Darlene , Brown-Johnson Cati , Asch Steven M. , Rosenthal Eben L. , Winget Marcy
Published: November 2019

PURPOSE:

Patients with cancer face daunting coordination problems at a vulnerable time. Lay navigation programs offer 1 approach to address these problems, but how to best implement these programs presents challenges. We sought to describe those implementation challenges at 1 academic cancer center to inform future efforts.

METHODS:

We performed a mixed methods study using standard implementation outcomes 1 year after program initiation. Quantitative data from the electronic medical record and qualitative data from in-depth interviews, focus groups, and ethnographic observations were included in analyses. The study took place at a National Cancer Institute–designated comprehensive cancer center across 12 tumor-specific clinics.

RESULTS:

Supportive care concerns, scheduling, and clinical-related issues were the most frequent issues navigators encountered. Effective navigation required continuous, time-consuming, invisible work, including building and maintaining a broad knowledge base of resources and health system processes, as well as cultivating relationships with diverse and changing clinical teams. The acceptability and appropriateness of lay navigator activities were mixed among clinic and social work staff, related to negotiating lines between clinical and nonclinical care.

CONCLUSION:

After 1 year of implementation, lay navigators still found it difficult to interpret and prioritize complex patient needs in a way that all clinical staff found appropriate. Negotiating these issues has made it difficult to develop the strong relationships with clinical teams that are needed for an integrated approach to patient care. To successfully coordinate patient care, it seems that lay navigation programs should be integrated with clinical teams to provide more seamless patient care.
Fabrication of Flexible Microsupercapacitors with Binder-Free ZIF-8 Derived Carbon Films via Electrophoretic Deposition
Authors: Li Yang , Henzie Joel , Park Teahoon , Wang Jie , Young Christine , Xie Huaqing , Yi Jin Woo , Li Jing , Kim Minjun , Kim Jeonghun , Yamauchi Yusuke , Na Jongbeom
Published: November 2019

Miniaturized power supplies, such as microsupercapacitors, are highly demanded in micro-electro mechanical systems (MEMS) and micro portable microdevices due to their superior cyclability, high power density, and considerable energy. In this study, we utilize ZIF-8 derived carbon as a source of active material to fabricate flexible microsupercapacitors via a simple electrophoresis method. The deposited ZIF-8 derived carbon particles with high surface area play a decisive role in achieving high electrochemical performances. The simple and straightforward process of electrophoretic deposition using ZIF-8 derived carbon particles generates porous carbon films on microsupercapacitors, which leads to a superior electrochemical performance.