bluuebunny/crossref_metadata_2025 huggingface dataset:
Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus
Authors: Lin Chu , Cai Xiaoling , Yang Wenjia , Lv Fang , Nie Lin , Ji Linong
Published: November 2020

Background

The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine.

Methods

Literature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, andClinicalTrials.govfor studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373.

Results

Significantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = − 0.12%, 95% CI, − 0.16 to − 0.07%) and weight reduction (ES = − 0.40 kg, 95% CI, − 0.50 to − 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = − 0.22%, 95% CI, − 0.32 to − 0.11%) versus oral types (ES = − 0.09%, 95% CI, − 0.14 to − 0.04%) in T2DM (P = 0.03). Older age (β = − 0.01, 95% CI, − 0.02 to − 0.01,P < 0.01) and longer diabetes duration (β = − 0.02, 95% CI, − 0.03 to − 0.21 × 10−2,P = 0.03) was significantly associated with more HbA1c reduction by placebo in T1DM. However, younger age (β = 0.02, 95% CI, 0.01 to 0.03,P = 0.01), lower male percentage (β = 0.01, 95% CI, 0.22 × 10−2, 0.01,P < 0.01), higher baseline BMI (β = − 0.02, 95% CI, − 0.04 to − 0.26 × 10−2,P = 0.02), and higher baseline HbA1c (β = − 0.09, 95% CI, − 0.16 to − 0.01,P = 0.02) were significantly associated with more HbA1c reduction by placebo in T2DM. Shorter diabetes duration (β = 0.06, 95% CI, 0.06 to 0.10,P < 0.01) was significantly associated with more weight reduction by placebo in T2DM. However, the associations between baseline BMI, baseline HbA1c, and placebo response were insignificant after the adjusted analyses.

Conclusion

The placebo response in diabetes mellitus was systematically outlined. Age, sex, disease severity (indirectly reflected by baseline BMI and baseline HbA1c), and disease duration were associated with placebo response in diabetes mellitus. The association between baseline BMI, baseline HbA1c, and placebo response may be the result of regression to the mean.
Use of electronic cigarettes and secondhand exposure to their aerosols are associated with asthma symptoms among adolescents: a cross-sectional study
Authors: Alnajem Abdullah , Redha Abdullah , Alroumi Dalal , Alshammasi Ahmed , Ali Mohamad , Alhussaini Maram , Almutairi Waad , Esmaeil Ali , Ziyab Ali H.
Published: November 2020

Background

Globally, a surge in electronic cigarette (e-cigarette) use has been observed in recent years, with youth being the most susceptible group. Given their recent emergence, studies assessing the health consequences of using e-cigarettes and exposure to their secondhand aerosols (SHA) are limited. Hence, this study sought to assess associations between e-cigarette use and household exposure to SHA from e-cigarettes with asthma symptoms among adolescents.

Methods

A school-based cross-sectional study was conducted by enrolling high school students (n = 1565; aged 16–19 years) in Kuwait. Participants self-completed a questionnaire on tobacco products use (e-cigarettes and cigarettes) and asthma symptoms. Current e-cigarette use and cigarette smoking were defined as any use in the past 30 days. Household exposure to SHA from e-cigarettes in the past 7 days was reported as none (0 days), infrequent (1–2 days), and frequent (≥ 3 days). Asthma symptoms included current (past 12 months) wheeze, current asthma (history of clinical diagnosis and current wheeze and/or medication use), and current symptoms of uncontrolled asthma (≥ 4 attacks of wheeze, ≥ 1 night per week sleep disturbance from wheeze, and/or wheeze affecting speech). Associations were assessed using Poisson regression with robust variance estimation, and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated.

Results

Among the analytical study sample (n = 1345), current e-cigarette use and cigarette smoking was reported by 369 (27.4%) and 358 (26.6%) participants, respectively. Compared to never e-cigarette users and never cigarette smokers, current e-cigarette users with no history of cigarette smoking had increased prevalence of current wheeze (aPR = 1.54, 95% CI 1.01–2.45) and current asthma (aPR = 1.85, 95% CI 1.03–3.41). Moreover, the frequency of exposure to household SHA from e-cigarettes was associated with asthma symptoms. For example, compared to those with no exposure to household SHA, frequent exposure to household SHA was associated with current wheeze (aPR = 1.30, 95% CI 1.04–1.59), current asthma (aPR = 1.56, 95% CI 1.13–2.16), and current uncontrolled asthma symptoms (aPR = 1.88, 95% CI 1.35–2.62).

Conclusions

E-cigarette use and their household SHA exposure were independently associated with asthma symptoms among adolescents. Hence, such observations indicate that e-cigarette use and passive exposure to their aerosols negatively impact respiratory health among adolescents.
Study design and operational framework for a community-based Malaria Elimination Demonstration Project (MEDP) in 1233 villages of district Mandla, Madhya Pradesh
Authors: Rajvanshi Harsh , Bharti Praveen K. , Nisar Sekh , Jain Yashpal , Jayswar Himanshu , Mishra Ashok K. , Sharma Ravendra K. , Saha Kalyan B. , Shukla Man Mohan , Das Aparup , Kaur Harpreet , Wattal Suman L. , Singh Neeru , Lal Altaf A.
Published: November 2020

Background

In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts.

Results

The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic.

Conclusion

This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.
Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers
Authors: Jarm Tomaz , Krmac Tadej , Magjarevic Ratko , Kos Bor , Cindric Helena , Miklavcic Damijan
Published: November 2020

Background

The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy?

Results

The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw.

Conclusions

The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.
Social inequalities in heat-attributable mortality in the city of Turin, northwest of Italy: a time series analysis from 1982 to 2018
Authors: Ellena Marta , Ballester Joan , Mercogliano Paola , Ferracin Elisa , Barbato Giuliana , Costa Giuseppe , Ingole Vijendra
Published: November 2020

Background

Understanding context specific heat-health risks in urban areas is important, especially given anticipated severe increases in summer temperatures due to climate change effects. We investigate social inequalities in the association between daily temperatures and mortality in summer in the city of Turin for the period 1982–2018 among different social and demographic groups such as sex, age, educational level, marital status and household occupants.

Methods

Mortality data are represented by individual all-cause mortality counts for the summer months between 1982 and 2018. Socioeconomic level and daily mean temperature were assigned to each deceased. A time series Poisson regression with distributed lag non-linear models was fitted to capture the complex nonlinear dependency between daily mortality and temperature in summer. The mortality risk due to heat is represented by the Relative Risk (RR) at the 99th percentile of daily summer temperatures for each population subgroup.

Results

All-cause mortality risk is higher among women (1.88; 95% CI = 1.77, 2.00) and the elderly (2.13; 95% CI = 1.94, 2.33). With regard to education, the highest significant effects for men is observed among higher education levels (1.66; 95% CI = 1.38, 1.99), while risks for women is higher for the lower educational level (1.93; 95% CI = 1.79, 2.08). Results on marital status highlighted a stronger association for widower in men (1.66; 95% CI = 1.38, 2.00) and for separated and divorced in women (2.11; 95% CI = 1.51, 2.94). The risk ratio of household occupants reveals a stronger association for men who lived alone (1.61; 95% CI = 1.39, 1.86), while for women results are almost equivalent between alone and not alone groups.

Conclusions

The associations between heat and mortality is unequal across different aspects of social vulnerability, and, inter alia, factors influencing the population vulnerability to temperatures can be related to demographic, social, and economic aspects. A number of issues are identified and recommendations for the prioritisation of further research are provided. A better knowledge of these effect modifiers is needed to identify the axes of social inequality across the most vulnerable population sub-groups.
Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study
Authors: Zou Wen , Wang Zehao , Xia Jing , Yang Jing
Published: November 2020

Background

Antioxidant/oxidant imbalance has been reported to be related to diminished ovarian reserve (DOR). Vitamin A (retinol), a kind of antioxidant, plays a role in restoring ovarian oxidative damage, while C-reactive protein (CRP) is the classical marker of oxidative stress and has recently been identified as an independent variable that is associated with low anti-Mullerian hormone (AMH) levels in young women with DOR. Additionally, retinol binding protein 4 (RBP4) can be considered a substitute for retinol in healthy, nonobese women. The study aim was to determine the relationship between serum RBP4, high sensitivity C-reactive protein (hs-CRP) concentrations and ovarian reserve in nonobese DOR patients.

Methods

This study included 24 DOR women and 48 normal ovarian reserve (NOR) women from the reproductive medical center of Renmin Hospital of Wuhan University. The serum RBP4 and high-sensitivity CRP (hs-CRP) levels were measured with ELISA kits.

Results

RBP4 levels (20,648.36 ± 5475.16 ng/ml vs 23,986.48 ± 5995.64 ng/ml,p = 0.025) were decreased, and hs-CRP levels (695.08 ± 1090.19 ng/ml vs 364.32 ± 786.29 ng/ml,p = 0.012) were increased in the DOR group. Serum RBP4 was positively related to AMH (Pearsonr = 0.518,p = 0.000), while hs-CRP was negatively correlated with AMH (Spearmanr = − 0.345,p = 0.005). after adjustments were made for the covariables, multiple line regression analysis showed that positive association between RBP4 and AMH still existed (β = 0.450,p< 0.001).

Conclusion

Decreased serum RBP4 levels and increased serum hs-CRP were observed in DOR patients in our study, and the strong correlation between RBP4 and AMH supports the notion that oxidative stress plays a role in DOR, and that appropriate levels of antioxidant vitamin A may be protective against ovarian reserve dysfunction.
Impact of changes in the methodology of external price referencing on medicine prices: discrete-event simulation
Authors: Vogler Sabine , Schneider Peter , Lepuschütz Lena
Published: November 2020

Background

Several governments apply the policy of external price referencing (EPR), which considers the prices of a medicine in one or more other countries for the purpose of setting the price in the own country. Different methodological choices can be taken to design EPR. The study aimed to analyse whether, or not, and how changes in the methodology of EPR can impact medicine prices.

Methods

The real-life EPR methodology as of Q1/2015 was surveyed in all European Union Member States (where applicable), Iceland, Norway and Switzerland through a questionnaire responded by national pricing authorities. Different scenarios were developed related to the parameters of the EPR methodology. Discrete-event simulations of fictitious prices in the 28 countries of the study that had EPR were run over 10 years. The continuation of the real-life EPR methodology in the countries as surveyed in 2015, without any change, served as base case.

Results

In most scenarios, after 10 years, medicine prices in all or most surveyed countries were—sometimes considerably—lower than in the base case scenario. But in a few scenarios medicine prices increased in some countries. Consideration of discounts (an assumed 20% discount in five large economies and the mandatory discount in Germany, Greece and Ireland) and determining the reference price based on the lowest price in the country basket would result in higher price reductions (on average − 47.2% and − 34.2% compared to the base case). An adjustment of medicine price data of the reference countries by purchasing power parities would lead to higher prices in some more affluent countries (e.g. Switzerland, Norway) and lower prices in lower-income economies (Bulgaria, Romania, Hungary, Poland). Regular price revisions and changes in the basket of reference countries would also impact medicine prices, however to a lesser extent.

Conclusions

EPR has some potential for cost-containment. Medicine prices could be decreased if certain parameters of the EPR methodology were changed. If public payers aim to apply EPR to keep medicine prices at more affordable levels, they are encouraged to explore the cost-containment potential of this policy by taking appropriate methodological choices in the EPR design.
Pelvic Ewing sarcoma: a retrospective outcome analysis of 104 patients who underwent pelvic tumor resection at a single supra-regional center
Authors: Guder Wiebke K. , Hardes Jendrik , Nottrott Markus , Steffen Anne Juliane , Dirksen Uta , Streitbürger Arne
Published: November 2020

Background

Local treatment in pelvic Ewing sarcoma (ES) consists of operation, radiation therapy, or a combination of both. Reported outcomes vary depending on the treatment modality performed. It is the objective of this study to analyze surgical outcome and complications as well as oncological outcome and complications of chemo- and radiation therapy in this patient cohort and evaluate prognostic factors.

Methods

Retrospective review of 104 patients who underwent tumor resection for pelvic ES from 1988 to 2014.

Results

All patients underwent pelvic resection and radiation therapy was administered in 77.9%. Margins were clear in 94.2%. The response to chemotherapy was good in 78.8%. Local recurrence occurred in 7.7%. The presence of distant metastases at the time of operation was the most important negative predictor for overall survival (p = 0.003). The cumulative 5- and 10-year survival rates were 82.7% and 80.1% for non-metastasized and 61.4% and 41.6% for metastasized pelvic ES at operation. In the presence of a single-distant metastatic site at operation compared to multiple metastatic sites, the cumulative survival rates were 64.3% versus 50% at five and 50.7% versus 16.7% at 10 years.

Conclusions

A combined treatment approach of tumor resection and radiation therapy leads to a local control and overall survival rates comparable with those of extremity locations in this study’s patient cohort with localized pelvic ES. Therefore, surgical tumor resection (combined with (neo-)adjuvant radiation therapy) in non-metastatic pelvic ES seems feasible. In metastatic patients, however, the significance of tumor resection as a part of local treatment remains less certain and improved outcomes of combined local treatment approaches need to be weighed against these patients’ prognosis and quality of life.
Tricuspid valve repair in isolated tricuspid pathology: a 12-year single center experience
Authors: Zubarevich Alina , Szczechowicz Marcin , Brcic Andreas , Osswald Anja , Tsagakis Konstantinos , Wendt Daniel , Schmack Bastian , Sá Michel Pompeu B. O. , Van den Eynde Jef , Ruhparwar Arjang , Zhigalov Konstantin
Published: November 2020

Objectives

Long-term data on isolated surgical tricuspid valve procedures is limited. Current guidelines on heart valve disease recommend valve repair over valve replacement. In this study we report our 12-year single-center experience with isolated surgical tricuspid valve repair in patients with various tricuspid valve pathologies.

Methods

Between May 2007 and December 2019, 26 consecutive patients underwent isolated tricuspid valve annuloplasty/repair for various indications. In 18 patients (69.2%) an open ring or band annuloplasty (26.9 and 42.3%, respectively) was performed, 5 patients (19.2%) underwent a tightening of the annulus using the DeVega technique, 5 patients (19.2%) had a leaflet reconstruction with patch or bicuspidalization and in 3 patients (11.5%) a leaflet debridement was performed. In 15.4% of the cohort a combination of the techniques was utilized.

Results

The mean follow-up time was 2.1 (0.3–5.0) years. Early survival at 30 days after surgery was 84.6%. Mean hospital stay was 11 (6.7–16) days. One-year survival was 73%. No patient required a redo procedure on the tricuspid valve during follow-up.

Conclusion

Tricuspid valve repair is suggested as a treatment of choice according to recent guidelines on heart valve disease. If chosen correctly, various repair techniques provide good long-term results. Tricuspid valve repair may be safely applied in patients undergoing surgical isolated tricuspid valve procedures.
Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides
Authors: Sacchini Flavio , Liljander Anne Mariana , Heller Martin , Poole Elizabeth Jane , Posthaus Horst , Schieck Elise , Jores Joerg
Published: November 2020

Contagious bovine pleuropneumonia (CBPP) is a respiratory disease caused by Mycoplasma mycoides subsp. mycoides. Infection occurs via Mycoplasma-containing droplets and therefore requires close contact between animals. The current infection models are suboptimal and based on intratracheal installation of mycoplasmas or in-contact infection. This work tested the infection of adult cattle via aerosols containing live mycoplasmas mimicking the infection of cattle in the field. Therefore, we infected six cattle with aerosolized Mycoplasma mycoides subsp. mycoides strain Afadé over seven consecutive days with altogether 109 colony forming units. All animals seroconverted between 11–24 days post infection and five out of six animals showed typical CBPP lesions. One animal did not show any lung lesions at necropsy, while another animal had to be euthanized at 25 days post infection because it reached endpoint criteria. Seroconversion confirmed successful infection and the spectrum of clinical and lesions observed mirrors epidemiological models and the field situation, in which only a fraction of animals suffers from acute clinical disease post infection.
Identification and characterization of satellite DNAs in Poa L.
Authors: Wei Linna , Liu Bo , Zhang Chunping , Yu Yang , Yang Xiaoxia , Dou Quanwen , Dong Quanmin
Published: November 2020

Background

Poa L. is a large genus of grass in Gramineae, among which P. pratensis is widely cultivated as turf and forage. Satellite DNA is the main components of the plant genome. Information of satellites will helpful for dissection the genome composition and definition of the phylogeny relationship of these species. However, the knowledge about the satellites in genus Poa is still limited.

Results

Four satellite DNAs were identified using the Repeat Explorer pipeline in HiSeq Illumina reads from diploid plants in P. malaca (2n = 26). Two satellites showed high similarity with the previously identified PpTr-1 and PpTr-3, whereas two others are newly identified with the monomer of 326 bp (Poa-326) and 353 bp (Poa-353) respectively. The clone DNAs of PpTr-1 and PpTr-3, and oligonucleotides designed representing satellites Poa-326 and Poa-353 were probed to test on chromosomes across 13 Poa speceis with different polyploidy level by fluorescent in situ hybridization (FISH). PpTr-1, PpTr-3, and Poa-362 were stably positioned in the subtelomeric regions in nearly all species with the variation of hybridization sites number. However, Poa-353 showed different FISH patterns of multiple regions with the variation of hybridization intensity and distribution sites across species. In addition, 5S rDNA and 45S rDNA were used to characterize the genome of the Poa species. Four rDNA FISH patterns were revealed in the tested species.

Conclusion

Four identified satellite were high conservable across Poa species. Genome distribution of these satellites can be characterized by FISH. The variation of satellite DNAs and rDNA chromosomal distributions between species provide useful information for phylogenetic analysis in genus Poa.
The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer
Authors: Colombo Carla , Minna Emanuela , Gargiuli Chiara , Muzza Marina , Dugo Matteo , De Cecco Loris , Pogliaghi Gabriele , Tosi Delfina , Bulfamante Gaetano , Greco Angela , Fugazzola Laura , Borrello Maria Grazia
Published: November 2020

Background

Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance.

Methods

We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAI-refractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness.

We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes.

Results

A different molecular profile according to the RAI class was observed: BRAFV600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAFV600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAFV600E than in gene fusions tumors.

Conclusions

The present data indicate a different molecular profile in RAI-avid and RAI-refractory metastatic PTCs. Moreover, BRAFV600E tumors displayed reduced differentiation and intrinsic RAI refractoriness, while PTCs with fusion oncogenes are RAI-avid but persistent, suggesting different oncogene-driven mechanisms leading to RAI refractoriness.
Host-adaptation of the rare Enterocytozoon bieneusi genotype CHN4 in Myocastor coypus (Rodentia: Echimyidae) in China
Authors: Yu Fuchang , Cao Yangwenna , Wang Haiyan , Liu Qiang , Zhao Aiyun , Qi Meng , Zhang Longxian
Published: November 2020

Background

Enterocytozoon bieneusi is a zoonotic gastrointestinal pathogen and can infect both humans and animals. The coypu (Myocastor coypus) is a semi-aquatic rodent, in which few E. bieneusi infections have been reported and the distribution of genotypes and zoonotic potential remains unknown.

Methods

A total of 308 fresh fecal samples were collected from seven coypu farms in China to determine the infection rate and the distribution of genotypes of E. bieneusi from coypus using nested-PCR amplification of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene.

Results

Enterocytozoon bieneusi was detected with an infection rate of 41.2% (n = 127). Four genotypes were identified, including three known genotypes (CHN4 (n = 111), EbpC (n = 8) and EbpA (n = 7)) and a novel genotype named CNCP1 (n = 1).

Conclusions

The rare genotype CHN4 was the most common genotype in the present study, and the transmission dynamics of E. bieneusi in coypus were different from other rodents. To the best of our knowledge, this is the first report of E. bieneusi infections in coypus in China. Our study reveals that E. bieneusi in coypus may be a potential infection source to humans.
DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial
Authors: Keller Maria , Yaskolka Meir Anat , Bernhart Stephan H. , Gepner Yftach , Shelef Ilan , Schwarzfuchs Dan , Tsaban Gal , Zelicha Hila , Hopp Lydia , Müller Luise , Rohde Kerstin , Böttcher Yvonne , Stadler Peter F. , Stumvoll Michael , Blüher Matthias , Kovacs Peter , Shai Iris
Published: November 2020

Background

One of the major challenges in obesity treatment is to explain the high variability in the individual’s response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.

Methods

We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m2) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity.

Results

Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change − 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10−5). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10− 4) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95–1.0] than predictors such as age and BMI (AUC ROC = 0.56).

Conclusions

Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.
Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review
Authors: Guo Hao-Yu , Guo Ming-Ke , Wan Zhong-Yuan , Song Fang , Wang Hai-Qiang
Published: November 2020

Intervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.
Enhanced differentiation of human pluripotent stem cells into pancreatic endocrine cells in 3D culture by inhibition of focal adhesion kinase
Authors: Liu Xiaofang , Qin Jinhua , Chang Mingyang , Wang Shuyong , Li Yali , Pei Xuetao , Wang Yunfang
Published: November 2020

Background

Generation of insulin-producing cells from human pluripotent stem cells (hPSCs) in vitro would be useful for drug discovery and cell therapy in diabetes. Three-dimensional (3D) culture is important for the acquisition of mature insulin-producing cells from hPSCs, but the mechanism by which it promotes β cell maturation is poorly understood.

Methods

We established a stepwise method to induce high-efficiency differentiation of human embryonic stem cells (hESCs) into mature monohormonal pancreatic endocrine cells (PECs), with the last maturation stage in 3D culture. To comprehensively compare two-dimensional (2D) and 3D cultures, we examined gene expression, pancreas-specific markers, and functional characteristics in 2D culture-induced PECs and 3D culture-induced PECs. The mechanisms were considered from the perspectives of cell–cell and cell–extracellular matrix interactions which are fundamentally different between 2D and 3D cultures.

Results

The expression of the pancreatic endocrine-specific transcription factors PDX1, NKX6.1, NGN3, ISL1, and PAX6 and the hormones INS, GCG, and SST was significantly increased in 3D culture-induced PECs. 3D culture yielded monohormonal endocrine cells, while 2D culture-induced PECs co-expressed INS and GCG or INS and SST or even expressed all three hormones. We found that focal adhesion kinase (FAK) phosphorylation was significantly downregulated in 3D culture-induced PECs, and treatment with the selective FAK inhibitor PF-228 improved the expression of β cell-specific transcription factors in 2D culture-induced PECs. We further demonstrated that 3D culture may promote endocrine commitment by limiting FAK-dependent activation of the SMAD2/3 pathway. Moreover, the expression of the gap junction protein Connexin 36 was much higher in 3D culture-induced PECs than in 2D culture-induced PECs, and inhibition of the FAK pathway in 2D culture increased Connexin 36 expression.

Conclusion

We developed a strategy to induce differentiation of monohormonal mature PECs from hPSCs and found limited FAK-dependent activation of the SMAD2/3 pathway and unregulated expression of Connexin 36 in 3D culture-induced PECs. This study has important implications for the generation of mature, functional β cells for drug discovery and cell transplantation therapy for diabetes and sheds new light on the signaling events that regulate endocrine specification.
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice
Authors: Arsenault Dany , Tremblay Cyntia , Emond Vincent , Calon Frédéric
Published: November 2020

While the higher prevalence of Alzheimer’s disease (AD) in women is clear, studies suggest that biological sex may also influence AD pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms. First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst afterhyperpolarization (AHP), and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas the paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar. In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.
Natural language processing algorithms for mapping clinical text fragments onto ontology concepts: a systematic review and recommendations for future studies
Authors: Kersloot Martijn G. , van Putten Florentien J. P. , Abu-Hanna Ameen , Cornet Ronald , Arts Derk L.
Published: November 2020

Background

Free-text descriptions in electronic health records (EHRs) can be of interest for clinical research and care optimization. However, free text cannot be readily interpreted by a computer and, therefore, has limited value. Natural Language Processing (NLP) algorithms can make free text machine-interpretable by attaching ontology concepts to it. However, implementations of NLP algorithms are not evaluated consistently. Therefore, the objective of this study was to review the current methods used for developing and evaluating NLP algorithms that map clinical text fragments onto ontology concepts. To standardize the evaluation of algorithms and reduce heterogeneity between studies, we propose a list of recommendations.

Methods

Two reviewers examined publications indexed by Scopus, IEEE, MEDLINE, EMBASE, the ACM Digital Library, and the ACL Anthology. Publications reporting on NLP for mapping clinical text from EHRs to ontology concepts were included. Year, country, setting, objective, evaluation and validation methods, NLP algorithms, terminology systems, dataset size and language, performance measures, reference standard, generalizability, operational use, and source code availability were extracted. The studies’ objectives were categorized by way of induction. These results were used to define recommendations.

Results

Two thousand three hundred fifty five unique studies were identified. Two hundred fifty six studies reported on the development of NLP algorithms for mapping free text to ontology concepts. Seventy-seven described development and evaluation. Twenty-two studies did not perform a validation on unseen data and 68 studies did not perform external validation. Of 23 studies that claimed that their algorithm was generalizable, 5 tested this by external validation. A list of sixteen recommendations regarding the usage of NLP systems and algorithms, usage of data, evaluation and validation, presentation of results, and generalizability of results was developed.

Conclusion

We found many heterogeneous approaches to the reporting on the development and evaluation of NLP algorithms that map clinical text to ontology concepts. Over one-fourth of the identified publications did not perform an evaluation. In addition, over one-fourth of the included studies did not perform a validation, and 88% did not perform external validation. We believe that our recommendations, alongside an existing reporting standard, will increase the reproducibility and reusability of future studies and NLP algorithms in medicine.
ParEst: joint estimation of the OFDM channel state information in MIMO systems
Authors: Zhang Zhenghao
Published: November 2020

OFDM channel state information (CSI) is needed for determining key parameters in MIMO transmissions. In this paper, a novel CSI estimation method, ParEst, is proposed, which estimates the CSI from multiple transmitting antennas simultaneously. ParEst is based on a recent discovery that the CSI can be approximated very well by the linear combination of complex-based sinusoids on constant frequencies. ParEst finds the CSI of all antennas jointly by solving an optimization problem and achieves higher accuracy than existing heuristic methods. As the base sinusoids are on constant frequencies, ParEst pre-computes most key steps and reduces the run-time computation complexity to just a modest number of vector dot products equivalent to a few FFT calculations. ParEst can be applied to MIMO links in networks such as LTE, 5G, or Wi-Fi.
Analysis and simulation of a mathematical model of tuberculosis transmission in Democratic Republic of the Congo
Authors: Kasereka Kabunga Selain , Doungmo Goufo Emile F. , Ho Tuong Vinh
Published: November 2020

According to the World Health Organization reports, tuberculosis (TB) remains one of the top 10 deadly diseases of recent decades in the world. In this paper, we present the modeling, analysis and simulation of a mathematical model of TB transmission in a population incorporating several factors and study their impact on the disease dynamics. The spread of TB is modeled by eight compartments including different groups, which are too often not taken into account in the projections of tuberculosis incidence. The rigorous mathematical analysis of this model is provided, the basic reproduction number ($\mathcal{R}_{0}$R0) is obtained and used for TB dynamics control. The results obtained show that lost to follow-up and transferred individuals constitute a risk, but less than the cases carrying germs. Rapidly evolving latent/exposed cases are responsible for the incidence increasing in the short and medium term, while slower evolving latent/exposed cases will be responsible for the persistent long-term incidence and maintenance of TB and delay elimination in the population. The numerical simulations of the model show that, with certain parameters, TB will die out or sensibly reduce in the entire Democratic Republic of the Congo (DRC) population. The strategies on which the DRC’s health system is currently based to fight this disease show their weaknesses because the TB situation in the DRC remains endemic. But monitoring contact, detection of latent individuals and their treatment are actions to be taken to reduce the incidence of the disease and thus effectively control it in the population.
A radiomics nomogram for the prediction of overall survival in patients with hepatocellular carcinoma after hepatectomy
Authors: Liu Qinqin , Li Jing , Liu Fei , Yang Weilin , Ding Jingjing , Chen Weixia , Wei Yonggang , Li Bo , Zheng Lu
Published: November 2020

Background

Hepatocellular carcinoma (HCC) is associated with a dismal prognosis, and prediction of the prognosis of HCC can assist in therapeutic decision-makings. An increasing number of studies have shown that the texture parameters of images can reflect the heterogeneity of tumors, and may have the potential to predict the prognosis of patients with HCC after surgical resection. The aim of this study was to investigate the prognostic value of computed tomography (CT) texture parameters in patients with HCC after hepatectomy and to develop a radiomics nomogram by combining clinicopathological factors and the radiomics signature.

Methods

In all, 544 eligible patients were enrolled in this retrospective study and were randomly divided into the training cohort (n = 381) and the validation cohort (n = 163). The tumor regions of interest (ROIs) were delineated, and the corresponding texture parameters were extracted. The texture parameters were selected by using the least absolute shrinkage and selection operator (LASSO) Cox model in the training cohort, and a radiomics signature was established. Then, the radiomics signature was further validated as an independent risk factor for overall survival (OS). The radiomics nomogram was established based on the Cox regression model. The concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomogram.

Results

The radiomics signature was formulated based on 7 OS-related texture parameters, which were selected in the training cohort. In addition, the radiomics nomogram was developed based on the following five variables: α-fetoprotein (AFP), platelet-to-lymphocyte ratio (PLR), largest tumor size, microvascular invasion (MVI) and radiomics score (Rad-score). The nomogram displayed good accuracy in predicting OS (C-index = 0.747) in the training cohort and was confirmed in the validation cohort (C-index = 0.777). The calibration plots also showed excellent agreement between the actual and predicted survival probabilities. The DCA indicated that the radiomics nomogram showed better clinical utility than the clinicopathologic nomogram.

Conclusion

The radiomics signature is a potential prognostic biomarker of HCC after hepatectomy. The radiomics nomogram that integrated the radiomics signature can provide a more accurate estimation of OS than the clinicopathologic nomogram for HCC patients after hepatectomy.
Recurrence hernia in the broad ligament of the uterus: a case report
Authors: Hashimoto Yoshifumi , Kanda Tatsuo , Chida Tadasu , Suda Kazuyoshi
Published: November 2020

Background

Bowel herniation through a defect in the broad ligament of the uterus is a rare disease and few cases of recurrence have been reported. We report herein a recurrence case of a patient with broad ligament hernia (BLH), along with a review of the literature.

Case presentation

A 53-year-old woman complaining of abdominal pain was transported to our hospital. She had a history of laparotomy for small-bowel obstruction associated with hernia in the broad ligament of the uterus 10 years ago at a local hospital. Abdominal pelvic contrast-enhanced computed tomography revealed that the mesentery of the dilated bowels converged at a thick band in the pelvis, suggesting closed loop obstruction of the small bowel. The patient underwent urgent laparotomy and was diagnosed with bowel herniation through an opening in the broad ligament of the uterus on the right side, which was ipsilateral with the previous surgery. The hernia orifice was widened by incision and incarcerated bowel segments were released and preserved because ischemia was reversible. The membranous defect of BLH was closed by suture with braded silk strings.

Conclusions

Although BLH is a rare disease, patients face a significant risk of disease recurrence. Nonabsorbable suture may be advisable for closure of the hernia orifice in BLH.