bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implications of incidental venous thromboembolism in cancer patients
Authors: Mulder Frits I. , Di Nisio Marcello , Ay Cihan , Carrier Marc , Bosch Floris T.M. , Segers Annelise , Kraaijpoel Noémie , Grosso Michael A. , Zhang George , Verhamme Peter , Wang Tzu-Fei , Weitz Jeffrey I. , Middeldorp Saskia , Raskob Gary , Beenen Ludo F.M. , Büller Harry R. , van Es Nick
Published: November 2019

Introduction

In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.

Methods

The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period.

Results

331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups.

Conclusion

Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.
The proteolytic activity of Listeria monocytogenes HtrA
Authors: Abfalter Carmen M. , Bernegger Sabine , Jarzab Miroslaw , Posselt Gernot , Ponnuraj Karthe , Wessler Silja
Published: November 2019

Background

High temperature requirement A (HtrA) is a widely expressed chaperone and serine protease in bacteria. HtrA proteases assemble and hydrolyze misfolded proteins to enhance bacterial survival under stress conditions. Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that induces listeriosis in humans. In previous studies, it was shown that deletion of htrA in the genome of L. monocytogenes increased the susceptibility to cellular stress and attenuated virulence. However, expression and protease activity of listerial HtrA (LmHtrA) were never analyzed in detail.

Results

In this study, we cloned LmHtrA wildtype (LmHtrAwt) and generated a proteolytic inactive LmHtrASA mutant. Recombinant LmHtrAwt and LmHtrASA were purified and the proteolytic activity was analyzed in casein zymography and in vitro cleavage assays. LmHtrA activity could be efficiently blocked by a small molecule inhibitor targeting bacterial HtrA proteases. The expression of LmHtrA was enhanced in the stationary growth phase of L. monocytogenes and significantly contributed to bacterial survival at high temperatures.

Conclusions

Our data show that LmHtrA is a highly active caseinolytic protease and provide a deeper insight into the function and mechanism, which could lead to medical and biotechnological applications in the future.
Functional characterization of a liverworts bHLH transcription factor involved in the regulation of bisbibenzyls and flavonoids biosynthesis
Authors: Zhao Yu , Zhang Yu-Ying , Liu Hui , Zhang Xiao-Shuang , Ni Rong , Wang Piao-Yi , Gao Shuai , Lou Hong-Xiang , Cheng Ai-Xia
Published: November 2019

Background

The basic helix-loop-helix (bHLH) transcription factors (TFs), as one of the largest families of TFs, play important roles in the regulation of many secondary metabolites including flavonoids. Their involvement in flavonoids synthesis is well established in vascular plants, but not as yet in the bryophytes. In liverworts, both bisbibenzyls and flavonoids are derived through the phenylpropanoids pathway and share several upstream enzymes.

Results

In this study, we cloned and characterized the function of PabHLH1, a bHLH family protein encoded by the liverworts speciesPlagiochasma appendiculatum. PabHLH1 is phylogenetically related to the IIIf subfamily bHLHs involved in flavonoids biosynthesis. A transient expression experiment showed that PabHLH1 is deposited in the nucleus and cytoplasm, while the yeast one hybrid assay showed that it has transactivational activity. When PabHLH1 was overexpressed inP. appendiculatumthallus, a positive correlation was established between the content of bibenzyls and flavonoids and the transcriptional abundance of corresponding genes involved in the biosynthesis pathway of these compounds. The heterologous expression of PabHLH1 inArabidopsis thalianaresulted in the activation of flavonoids and anthocyanins synthesis, involving the up-regulation of structural genes acting both early and late in the flavonoids synthesis pathway. The transcription level of PabHLH1 inP. appendiculatumthallus responded positively to stress induced by either exposure to UV radiation or treatment with salicylic acid.

Conclusion

PabHLH1 was involved in the regulation of the biosynthesis of flavonoids as well as bibenzyls in liverworts and stimulated the accumulation of the flavonols and anthocyanins in Arabidopsis.
Dynamic predictive accuracy of electrocardiographic biomarkers of sudden cardiac death within a survival framework: the Atherosclerosis Risk in Communities (ARIC) study
Authors: Perez-Alday Erick A. , Bender Aron , German David , Mukundan Srini V. , Hamilton Christopher , Thomas Jason A. , Li-Pershing Yin , Tereshchenko Larisa G.
Published: November 2019

Background

The risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD).

Methods

Atherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n = 15,716; 55% female, 73% white, age 54.2 ± 5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was the competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using a survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured.

Results

Over a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63–1.91)/1000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37–2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526–0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303–0.75). SVG elevation more accurately predicted SCD if the ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526–0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515–0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% of SCD events were reclassified from low or intermediate risk to a high-risk category. QRS-T angle was the strongest long-term predictor of SCD (AUC 0.710; 95%CI 0.668–0.753 for ECG recorded within 10 years before SCD).

Conclusion

Short-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.
Age at menarche and risk of multiple sclerosis (MS): a systematic review and meta-analysis
Authors: Azimi Amirreza , Hanaei Sara , Sahraian Mohammad Ali , Mohammadifar Mehdi , Ramagopalan Sreeram V. , Ghajarzadeh Mahsa
Published: November 2019

Background

Some studies have looked at the age at menarche and risk of Multiple Sclerosis (MS).We aimed to conduct a systematic review and meta-analysis to estimate a pooled odds ratio of developing MS by increasing age at menarche.

Methods

We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, google scholar and gray literature (references of references, congress abstracts) up to 10th April 2019.

Results

The literature search found 312 articles. After eliminating duplicates, reviews, case reports and trials, 18 articles remained. Three articles were ultimately included in the final analysis. Two studies were from Iran, and one from Canada. The pooled odds ratio (OR) for increasing 1 year of age at menarche was 0.88 (95% CI:0.82-0.94), with no significant heterogeneity (I2 = 49%, p = 0.1). Mean age at menarche was significantly different between case and control groups (mean difference = − 0.22, 95% CI = -0.42,-0.02).

Conclusion

The result of this systematic review showed that the risk of MS decreases by increasing age at menarche.
Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases - a single-center retrospective analysis
Authors: Li Zhensheng , Shen Dongxing , Zhang Jian , Zhang Jun , Yang Fang , Kong Deyou , Kong Jie , Zhang Andu
Published: November 2019

Background

The relationship between whole brain radiotherapy (WBRT) dose with intracranial tumor control and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) brain metastases (BM) is largely unknown.

Methods

We retrospectively analyzed 595 NSCLC BM patients treated consecutively at the Fourth Hospital of Hebei Medical University between 2013 to 2015. We assigned the patients into 4 dose groups of WBRT: none, < 30, 30–39, and ≥ 40 Gy and assessed their relationship with OS and intracranial progression-free survival (iPFS). Cox models were utilized. Covariates included sex, age, KPS, BM lesions, extracranial metastasis, BM and lung tumor resection, chemotherapy, targeted therapy, and focal radiotherapy modalities.

Results

Patients had a mean age of 59 years and were 44% female. Their median survival time (MST) of OS and iPFS were 9.3 and 8.9 months. Patients receiving none (344/58%), < 30 (30/5%), 30–39 (93/16%), and ≥ 40 (128/22%) Gy of WBRT had MST of OS (iPFS) of 7.3 (6.8), 6.0 (5.4), 10.3 (11.9) and 11.9 (11.9) months, respectively. Compared to none, other WBRT groups had adjusted HRs for OS - 1.23 (p > 0.20), 0.72 (0.08), 0.61 (< 0.00) and iPFS - 1.63 (0.03), 0.71 (0.06), 0.67 (< 0.01). Compared to 30–39 Gy, WBRT dose ≥40 Gy was not associated with improved OS and iPFS (all p > 0.40). Stratified analyses by 1–3 and ≥ 4 BM lesions and adjustment analyses by each prognostic index of RPA class, Lung-GPA and Lung-molGPA supported these relationships as well.

Conclusions

Compared to none, WBRT doses ≥30 Gy are invariably associated with improved intracranial tumor control and survival in NSCLC BM patients.
Anxiety at age 15 predicts psychiatric diagnoses and suicidal ideation in late adolescence and young adulthood: results from two longitudinal studies
Authors:   NTR, Doering Sabrina , Lichtenstein Paul , Gillberg Christopher , Middeldorp Christel M. , Bartels Meike , Kuja-Halkola Ralf , Lundström Sebastian
Published: November 2019

Background

Anxiety disorders in adolescence have been associated with several psychiatric outcomes. We sought to describe the prospective relationship between various levels of adolescent anxiety and psychiatric diagnoses (anxiety-, bipolar/psychotic-, depressive-, and alcohol and drug misuse disorders) and suicidal ideation in early adulthood while adjusting for childhood attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, we aimed to estimate the proportion attributable to the various anxiety levels for the outcomes.

Methods

We used a nation-wide population-based Swedish twin study comprising 14,106 fifteen-year-old twins born in Sweden between 1994 and 2002 and a replication sample consisting of 9211 Dutch twins, born between 1985 and 1999. Adolescent anxiety was measured with parental and self-report. Psychiatric diagnoses and suicidal ideation were retrieved from the Swedish National Patient Register and via self-report.

Results

Adolescent anxiety, of various levels, predicted, in the Swedish National Patient Register, anxiety disorders: hazard ratio (HR) = 4.92 (CI 3.33–7.28); depressive disorders: HR = 4.79 (3.23–7.08), and any psychiatric outcome: HR = 3.40 (2.58–4.48), when adjusting for ADHD, ASD, and DCD. The results were replicated in the Dutch data. The proportion of psychiatric outcome attributable to adolescent anxiety over time (age 15–21) was 29% for any psychiatric outcome, 43–40% for anxiety disorders, and 39–38% for depressive disorders.

Conclusion

Anxiety in adolescence constitutes an important risk factor in the development of psychiatric outcomes, revealing unique predictions for the different levels of anxiety, and beyond the risk conferred by childhood ADHD, ASD, and DCD. Developmental trajectories leading into psychiatric outcomes should further empirically investigated.
Engineering cytoplasmic acetyl-CoA synthesis decouples lipid production from nitrogen starvation in the oleaginous yeast Rhodosporidium azoricum
Authors: Donzella Silvia , Cucchetti Daniela , Capusoni Claudia , Rizzi Aurora , Galafassi Silvia , Chiara Gambaro , Compagno Concetta
Published: November 2019

Background

Oleaginous yeasts are able to accumulate very high levels of neutral lipids especially under condition of excess of carbon and nitrogen limitation (medium with high C/N ratio). This makes necessary the use of two-steps processes in order to achieve high level of biomass and lipid. To simplify the process, the decoupling of lipid synthesis from nitrogen starvation, by establishing a cytosolic acetyl-CoA formation pathway alternative to the one catalysed by ATP-citrate lyase, can be useful.

Results

In this work, we introduced a new cytoplasmic route for acetyl-CoA (AcCoA) formation inRhodosporidium azoricumby overexpressing genes encoding for homologous phosphoketolase (Xfpk) and heterologous phosphotransacetylase (Pta). The engineered strain PTAPK4 exhibits higher lipid content and produces higher lipid concentration than the wild type strain when it was cultivated in media containing different C/N ratios. In a bioreactor process performed on glucose/xylose mixture, to simulate an industrial process for lipid production from lignocellulosic materials, we obtained an increase of 89% in final lipid concentration by the engineered strain in comparison to the wild type. This indicates that the transformed strain can produce higher cellular biomass with a high lipid content than the wild type. The transformed strain furthermore evidenced the advantage over the wild type in performing this process, being the lipid yields 0.13 and 0.05, respectively.

Conclusion

Our results show that the overexpression of homologous Xfpk and heterologous Pta activities inR. azoricumcreates a new cytosolic AcCoA supply that decouples lipid production from nitrogen starvation. This metabolic modification allows improving lipid production in cultural conditions that can be suitable for the development of industrial bioprocesses using lignocellulosic hydrolysates.
The assessment of xenogeneic bone immunotoxicity and risk management study
Authors: Sun Xiaoxia , Liu Chenghu , Shi Yanping , Li Chunling , Sun Likui , Hou Li , Wang Xin
Published: November 2019

Background

Xenogeneic bone has been widely used in a variety of clinical bone-related disease to promote bone healing and restore bone defects. However, the adverse effects of immune system limit its application in the clinic. The aim of this study was to evaluate xenogeneic bone safety of immunotoxicity and explore the methods for immune risk supervision.

Results

Xenogeneic bone, which is freeze-dried bovine cancellous bone, was implanted into the muscle of mice. On day 7, 14 and 28, the effects of xenogeneic bone were examined on humoral immunity and cellular immunity, including the levels of IgG, IgM, C3, inflammatory factors (TNF-α, IL-6), alkaline phosphatase (ALP) and the lymphocyte phenotype. The data showed that xenogeneic bone implantation had no potential to induce immune responses not only in humoral immunity but also in cellular immunity. To reveal the risk of immunogenicity, the residual DNA and the clearance of α-gal epitope were analyzed in 2 different bones (bone 1 is deproteinized bone, bone 2 is acellular and defatted bone). It was suggested that DNA of xenogeneic bone can be limited to < 50 ng per mg dry weight for the repair or regeneration with the acceptable immune risk. And α-gal clearance of xenogeneic bone could be an effective risk factor for improving xenograft quality management.

Conclusions

Through the detection of xenogeneic bone immunotoxicity, our findings indicated that the supervisions of risk factors could contribute to reduce the immune risk. And the risk factors under the acceptable limitation could decrease or replace animal experiment. However, it still needs to be studied on the limitation of α-gal epitope to predict rejection of xenogeneic bone more accurately.
Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke
Authors: Salmeron Kathleen E. , Maniskas Michael E. , Edwards Danielle N. , Wong Raymond , Rajkovic Ivana , Trout Amanda , Rahman Abir A. , Hamilton Samantha , Fraser Justin F. , Pinteaux Emmanuel , Bix Gregory J.
Published: November 2019

Background

Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016).

Methods

Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses.

Results

We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair.

Conclusions

Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.
Development of caesarean section prediction models: secondary analysis of a prospective cohort study in two sub-Saharan African countries
Authors: de Souza Hayala C. C. , Perdoná Gleici S. C. , Marcolin Alessandra C. , Oyeneyin Lawal O. , Oladapo Olufemi T. , Mugerwa Kidza , Souza João Paulo
Published: November 2019

Background

Caesarean section is recommended in situations in which vaginal birth presents a greater likelihood of adverse maternal or perinatal outcomes than normal. However, it is associated with a higher risk of complications, especially when performed without a clear medical indication. Since labour attendants have no standardised clinical method to assist in this decision, statistical tools developed based on multiple labour variables may be an alternative. The objective of this paper was to develop and evaluate the accuracy of models for caesarean section prediction using maternal and foetal characteristics collected at admission and through labour.

Method

This is a secondary analysis of the World Health Organization’s Better Outcomes in Labour Difficulty prospective cohort study in two sub-Saharan African countries. Data were collected from women admitted for labour and childbirth in 13 hospitals in Nigeria as well as Uganda between 2014 and 2015. We applied logistic regression to develop different models to predict caesarean section, based on the time when intrapartum assessment was made. To evaluate discriminatory capacity of the various models, we calculated: area under the curve, diagnostic accuracy, positive predictive value, negative predictive value, sensitivity and specificity.

Results

A total of 8957 pregnant women with 12.67% of caesarean births were used for model development. The model based on labour admission characteristics showed an area under the curve of 78.70%, sensitivity of 63.20%, specificity of 78.68% and accuracy of 76.62%. On the other hand, the models that applied intrapartum assessments performed better, with an area under the curve of 93.66%, sensitivity of 80.12%, specificity of 89.26% and accuracy of 88.03%.

Conclusion

It is possible to predict the likelihood of intrapartum caesarean section with high accuracy based on labour characteristics and events. However, the accuracy of this prediction is considerably higher when based on information obtained throughout the course of labour.
Characterizing the composition, metabolism and physiological functions of the fatty liver in Rana omeimontis tadpoles
Authors: Zhu Wei , Zhang Meihua , Chang Liming , Zhu Wenbo , Li Cheng , Xie Feng , Zhang Huan , Zhao Tian , Jiang Jianping
Published: November 2019

Background

Fat storage is required for the life cycle of many organisms. The primary fat depot for most vertebrates is white adipose tissue. However, in primitive vertebrates (e.g., agnathan group and elasmobranchs), the liver is usually responsible for fat storage. Among the vertebrates, amphibians have a unique status, as their larvae live in the water and exhibit some primitive traits that are similar to fish. Although it has been recognized that adult frogs use their abdominal white adipose tissue as a primary fat depot, how tadpoles store their fat is still inconclusive. The metabolic traits and physiological functions of primitive fat depots may have wide-ranging implications on the pathology of abnormal lipid deposition in mammals and the evolution of fat storage.

Results

Rana omeimontis tadpoles used their liver as the primary fat depot. In sufficiently fed tadpoles at stage 30–31, the hepatosomatic index (HSI) reached up to 7%, and triglycerides (TG) accounted for 15% of liver weight. Their liver resembled white adipose tissue in histological morphology, characterized by polygonal hepatocytes filled with fat. Their liver metabolic composition was unique, characterized by the dominance of maltotriose, arachidonic acid and dipeptides in soluble carbohydrates, free fatty acids and amino acids. Hepatic fat was the major metabolic fuel of fasted R. omeimontis tadpoles, which had similar reserve mobilization and allocation patterns as mammals. From a developmental perspective, hepatic fat was important to fuel late metamorphic climax. Interestingly, starvation induced accelerated metamorphosis in tadpoles with high HSI (4.96 ± 0.21%). However, this phenomenon was not observed in tadpoles with low HSI (2.71 ± 0.16%), even though they had similar initial body weight and developmental stage. Hepatic fat abundance was the most prominent difference between the two groups.

Conclusion

To the best of our knowledge, this is the first report that liver can be the primary fat depot in vertebrates with higher evolutionary status than bony fish. The unique hepatic histological and metabolic traits likely either guard their liver against lipotoxicity or make their hepatocytes adapt to fat accumulation. This fatty liver could be a primitive counterpart of mammalian white adipose tissue (WAT). In addition, our study showed that the hepatic reserves of tadpoles, especially TG content, may provide body condition signals to modulate metamorphosis.
The mechanism of miR-889 regulates osteogenesis in human bone marrow mesenchymal stem cells
Authors: Xu Gang , Ding Zheng , Shi Hui-feng
Published: November 2019

Background

Bone marrow mesenchymal stem cells (BMMSCs) can be used for bone regeneration in the specified condition. Osteogenic differentiation of BMMSCs is controlled by microRNAs (miRNAs) and other factors. This study was aimed to identify the role and mechanism of miR-889 in regulating the osteogenic differentiation of BMMSCs.

Methods

Osteoporosis patients and normal control bone tissues were collected and used PCR techniques to identify the change of miR-889 and WNT7A. Moreover, the dynamic change of miR-889 and WNT7A during osteogenic differentiation of BMMSCs was also measured. Bioinformatic analysis was performed to identify the target genes and potential pathways of miR-889. Then, we constructed miR-889 mimic and inhibitor, ALP staining, ARS, osteoblastic-related protein, and Wnt β-catenin signaling pathway-related protein were also measured. WNT7A siRNA was also used to verify the function of miR-889.

Results

In the present study, we showed that miR-889 expression was upregulated in osteoporosis patients than healthy control. However, the miR-889 expression was downregulated during osteogenic differentiation. Bioinformatics analysis found that miR-889 targets 666 genes and mainly through Wnt β-catenin signaling pathway. Administrated miR-889 mimic, the ALP activity, and calcium deposition were decreased than the control group, while miR-889 inhibitor shown the opposite trend. And miR-889 could bind the 3′UTR of WNT7A. We further used WNT7A siRNA to explore the function of miR-889, and the results revealed that co-cultured with miR-889 inhibitor and WNT7A siRNA was associated with a reduction of ALP activity and calcium deposition and osteoblastic-related proteins than miR-889 inhibitor alone.

Conclusion

Our results revealed that miR-889 plays a negative role in inducing osteogenic differentiation of BMSCs through Wnt β-catenin signaling pathway.
Pubertal timing and breast density in young women: a prospective cohort study
Authors: Houghton Lauren C. , Jung Seungyoun , Troisi Rebecca , LeBlanc Erin S. , Snetselaar Linda G. , Hylton Nola M. , Klifa Catherine , Van Horn Linda , Paris Kenneth , Shepherd John A. , Hoover Robert N. , Dorgan Joanne F.
Published: November 2019

Background

Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.

Methods

From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.

Results

The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (ptrend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (ptrend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)).

Conclusions

Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.
NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION
Authors: De Roeck Arne , De Coster Wouter , Bossaerts Liene , Cacace Rita , De Pooter Tim , Van Dongen Jasper , D’Hert Svenn , De Rijk Peter , Strazisar Mojca , Van Broeckhoven Christine , Sleegers Kristel
Published: November 2019

Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer’s disease-associatedABCA7VNTR. The Guppy “flip-flop” base caller and tandem-genotypes tandem repeat caller are efficient for large-scale tandem repeat assessment, but base calling and alignment challenges persist. We present NanoSatellite, which analyzes tandem repeats directly on electric current data and improves calling of GC-rich tandem repeats, expanded alleles, and motif interruptions.
Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway
Authors: Wang Hui , Zhang Chuan-Shan , Fang Bin-Bin , Li Zhi-De , Li Liang , Bi Xiao-Juan , Li Wen-Ding , Zhang Ning , Lin Ren-Yong , Wen Hao
Published: November 2019

Background

Larvae ofEchinococcus granulosus(sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced byE. granulosus(s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear.

Methods

The activation status of peritoneal macrophages (PMs) derived from mice infected withE. granulosus(sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treatedin vivoandin vitrowith recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected.

Results

The expression of AAM-related genes in PMs was preferentially induced afterE. granulosus(s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated fromE. granulosus(s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained afterE. granulosus(s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotypein vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor.

Conclusions

This study demonstrates thatE. granulosus(s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part,viathe PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.
Spatial–temporal distribution of Aedes (Stegomyia) aegypti and locations of recycling units in southeastern Brazil
Authors: Piovezan Rafael , Visockas Alexandre , de Azevedo Thiago Salomão , Von Zuben Cláudio José , Sallum Maria Anice Mureb
Published: November 2019

Background

Dengue is an arbovirus disease that threatens approximately 200 million people annually worldwide. Aedes (Stegomyia) aegypti (Linnaeus, 1762) is anthropophilic mosquito, extremely well adapted to the urban environment and utilizes varied habitats for egg-laying and development. This study analysed the distribution of mosquito larvae and eggs in urban area of Santa Bárbara dʼOeste, São Paulo, Brazil. The spatial correlation between locations in which people store recyclable materials and the distribution of larvae and eggs were verified.

Methods

Larvae and ovitrap egg collections were conducted from 2014 to 2016. All persons who stored recyclable materials for living were registered and georeferenced. The Mann-Kendall test was used to verify spatial and temporal trends in the number of eggs and larvae/pupae. Euclidian distance map was constructed to correlate recyclable collectors and Ae. aegypti, and Moranʼs index was employed to verify their spatial autocorrelation and identification of groupings.

Results

A total of 137,825 eggs and 16,393 larvae were collected in different habitats from 2014 to 2016. The analyses showed that there was a spatial correlation between larvae and eggs collected, and these two kinds of surveys also presented a spatial correlation with the handling of recyclable materials. The results of the analyses showed significant spatial correlations between eggs and recyclable material collectors and between larvae and collectors.

Conclusion

The entomological surveillance conducted using ovitraps as a proxy for the presence of Ae. aegypti is an efficient and sensitive method for monitoring the presence of mosquitoes and the impact of interventions employed for decreasing vector populations. Mosquito surveys employing ovitraps should be used more often in routine activities aiming to control dengue through vector control interventions. The locations used to store recyclable materials have a significant relationship with the maintenance of the dengue virus infection in the area. Further studies will be needed to analyse the contribution of recyclable locations, for which there is no ideal infrastructure to minimize the potential use of these materials as mosquito habitats. The entomological surveillance focused on locations of recyclable materials involving interventions that are different from those commonly used in Ae. aegypti control.
Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer—a clinical biomarker discovery and validation study
Authors: Jensen Sarah Østrup , Øgaard Nadia , Ørntoft Mai-Britt Worm , Rasmussen Mads Heilskov , Bramsen Jesper Bertram , Kristensen Helle , Mouritzen Peter , Madsen Mogens Rørbæk , Madsen Anders Husted , Sunesen Kåre Gotschalck , Iversen Lene Hjerrild , Laurberg Søren , Christensen Ib Jarle , Nielsen Hans Jørgen , Andersen Claus Lindbjerg
Published: November 2019

Background

Early detection plays an essential role to reduce colorectal cancer (CRC) mortality. While current screening methods suffer from poor compliance, liquid biopsy-based strategies for cancer detection is rapidly gaining promise. Here, we describe the development of TriMeth, a minimal-invasive blood-based test for detection of early-stage colorectal cancer. The test is based on assessment of three tumour-specific DNA methylation markers in circulating cell-free DNA.

Results

A thorough multi-step biomarker discovery study based on DNA methylation profiles of more than 5000 tumours and blood cell populations identified CRC-specific DNA methylation markers. The DNA methylation patterns of biomarker candidates were validated by bisulfite sequencing and methylation-specific droplet digital PCR in CRC tumour tissue and peripheral blood leucocytes. The three best performing markers were first applied to plasma from 113 primarily early-stage CRC patients and 87 age- and gender-matched colonoscopy-verified controls. Based on this, the test scoring algorithm was locked, and then TriMeth was validated in an independent cohort comprising 143 CRC patients and 91 controls. Three DNA methylation markers, C9orf50, KCNQ5, and CLIP4, were identified, each capable of discriminating plasma from colorectal cancer patients and healthy individuals (areas under the curve 0.86, 0.91, and 0.88). When combined in the TriMeth test, an average sensitivity of 85% (218/256) was observed (stage I: 80% (33/41), stage II: 85% (121/143), stage III: 89% (49/55), and stage IV: 88% (15/17)) at 99% (176/178) specificity in two independent plasma cohorts.

Conclusion

TriMeth enables detection of early-stage colorectal cancer with high sensitivity and specificity. The reported results underline the potential utility of DNA methylation-based detection of circulating tumour DNA in the clinical management of colorectal cancer.
Giant parathyroid adenoma: a case report and review of the literature
Authors: Al-Hassan Mohamed S. , Mekhaimar Menatalla , El Ansari Walid , Darweesh Adham , Abdelaal Abdelrahman
Published: November 2019

Background

Giant parathyroid adenoma is a rare type of parathyroid adenoma defined as weighing > 3.5 g. They present as primary hyperparathyroidism but with more elevated laboratory findings and more severe clinical presentations due to the larger tissue mass. This is the first reported case of giant parathyroid adenoma from the Middle East.

Case presentation

A 52-year-old Indian woman presented with a palpable right-sided neck mass and generalized fatigue. Investigations revealed hypercalcemia with elevated parathyroid hormone and an asymptomatic kidney stone. Ultrasound showed a complex nodule with solid and cystic components, and Sestamibi nuclear scan confirmed a giant parathyroid adenoma. Focused surgical neck exploration was done and a giant parathyroid adenoma weighing 7.7 gm was excised.

Conclusions

Giant parathyroid adenoma is a rare cause of primary hyperparathyroidism and usually presents symptomatically with high calcium and parathyroid hormone levels. Giant parathyroid adenoma is diagnosed by imaging and laboratory studies. Management is typically surgical, aiming at complete resection. Patients usually recover with no long-term complications or recurrence.
Greedy low-rank algorithm for spatial connectome regression
Authors: Kürschner Patrick , Dolgov Sergey , Harris Kameron Decker , Benner Peter
Published: November 2019

Recovering brain connectivity from tract tracing data is an important computational problem in the neurosciences. Mesoscopic connectome reconstruction was previously formulated as a structured matrix regression problem (Harris et al. in Neural Information Processing Systems, 2016), but existing techniques do not scale to the whole-brain setting. The corresponding matrix equation is challenging to solve due to large scale, ill-conditioning, and a general form that lacks a convergent splitting. We propose a greedy low-rank algorithm for the connectome reconstruction problem in very high dimensions. The algorithm approximates the solution by a sequence of rank-one updates which exploit the sparse and positive definite problem structure. This algorithm was described previously (Kressner and Sirković in Numer Lin Alg Appl 22(3):564–583, 2015) but never implemented for this connectome problem, leading to a number of challenges. We have had to design judicious stopping criteria and employ efficient solvers for the three main sub-problems of the algorithm, including an efficient GPU implementation that alleviates the main bottleneck for large datasets. The performance of the method is evaluated on three examples: an artificial “toy” dataset and two whole-cortex instances using data from the Allen Mouse Brain Connectivity Atlas. We find that the method is significantly faster than previous methods and that moderate ranks offer a good approximation. This speedup allows for the estimation of increasingly large-scale connectomes across taxa as these data become available from tracing experiments. The data and code are available online.
Optimization of agro-residues as substrates for Pleurotus pulmonarius production
Authors: Wu Nan , Tian Fenghua , Moodley Odeshnee , Song Bing , Jia Chuanwen , Ye Jianqiang , Lv Ruina , Qin Zhi , Li Changtian
Published: November 2019

The “replacing wood by grass” project can partially resolve the conflict between mushroom production and balancing the ecosystem, while promoting agricultural economic sustainability.Pleurotus pulmonariusis an economically important edible and medicinal mushroom, which is traditionally produced using a substrate consisting of sawdust and cottonseed hulls, supplemented with wheat bran. A simplex lattice design was applied to systemically optimize the cultivation ofP. pulmonariususing agro-residues as the main substrate to replace sawdust and cottonseed hulls. The effects of differing amounts of wheat straw, corn straw, and soybean straw on the variables of yield, mycelial growth rate, stipe length, pileus length, pileus width, and time to harvest were demonstrated. Results indicated that a mix of wheat straw, corn straw, and soybean straw may have significantly positive effects on each of these variables. The high yield comprehensive formula was then optimized to include 40.4% wheat straw, 20.3% corn straw, 18.3% soybean straw, combined with 20.0% wheat bran, and 1.0% light CaCO3(C/N = 42.50). The biological efficiency was 15.2% greater than that of the control. Most encouraging was the indication that the high yield comprehensive formula may shorten the time to reach the reproductive stage by 6 days, compared with the control. Based on the results of this study, agro-residues may be used as a suitable substitution for sawdust and cottonseed hulls as the main cultivation substrates ofP. pulmonarius. These results provide a theoretical basis for the “replacing wood by grass” project on edible mushroom cultivation.
Development of a multiplex PCR assay for the simultaneous and rapid detection of six pathogenic bacteria in poultry
Authors: Wang Zhihao , Zuo Jiakun , Gong Jiansen , Hu Jiangang , Jiang Wei , Mi Rongsheng , Huang Yan , Chen Zhaoguo , Phouthapane Vanhnaseng , Qi Kezong , Wang Chen , Han Xiangan
Published: November 2019

Escherichia coli, Pasteurella multocida, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Staphylococcus aureus are six bacterial pathogens of avian. However, these pathogens may cause many similar pathological changes, resulting in clinical isolates that are difficult to quickly and simultaneously detect and identify. Here, a multiplex polymerase chain reaction (m-PCR) assay is reported to rapidly identify targets genes (phoA, KMT1, ureR, toxA, invA, and nuc) of these six pathogens in clinical samples. Six pairs of specific primers were designed. The optimal reaction conditions, specificity, and sensitivity of the m-PCR assay were investigated. The results showed that betaine remarkably improved amplification of the target genes. Specific test results showed that all six pathogens were detected by the proposed m-PCR protocol without cross-amplification with viruses or parasites. Sensitivity test results showed that the m-PCR system could amplify the six target genes from bacterial genomes or cultures with template amounts of 500 pg or 2.8–8.6 × 103 colony forming units, respectively. Furthermore, the six bacterial pathogens isolated from the infected tissue samples were successfully identified. The proposed m-PCR assay is a useful tool to monitor and diagnose bacterial infection in birds with high specificity, sensitivity and throughput.
Some Opial-type integral inequalities via $(p,q)$-calculus
Authors: Nasiruzzaman Md. , Mukheimer Aiman , Mursaleen M.
Published: November 2019

In this paper, we introduce a new Opial-type inequality by using$(p,q)$(p,q)-calculus and establish some integral inequalities. We find a$(p,q)$(p,q)-generalization of a Steffensens-type integral inequality and some other inequalities.
Schur-harmonic convexity related to co-ordinated harmonically convex functions in plane
Authors: Safaei N. , Barani A.
Published: November 2019

In this paper, we investigate Schur-harmonic convexity of some functions which are obtained from the co-ordinated harmonically convex functions on a square in a plane.
On statistical convergence and strong Cesàro convergence by moduli
Authors: León-Saavedra Fernando , Listán-García M. del Carmen , Pérez Fernández Francisco Javier , Romero de la Rosa María Pilar
Published: November 2019

In this paper we will establish a result by Connor, Khan and Orhan (Analysis 8:47–63, 1988; Publ. Math. (Debr.) 76:77–88, 2010) in the framework of the statistical convergence and the strong Cesàro convergence defined by a modulus functionf. Namely, for every modulus functionf, we will prove that af-strongly Cesàro convergent sequence is alwaysf-statistically convergent and uniformly integrable. The converse of this result is not true even for bounded sequences. We will characterize analytically the modulus functionsffor which the converse is true. We will prove that these modulus functions are those for which the statistically convergent sequences aref-statistically convergent, that is, we show that Connor–Khan–Orhan’s result is sharp in this sense.
Oscillatory behavior of a second order nonlinear advanced differential equation with mixed neutral terms
Authors: Shi Hongwei , Bai Yuzhen
Published: November 2019

In this paper, we present several new oscillation criteria for a second order nonlinear differential equation with mixed neutral terms of the form
$$ \bigl(r(t) \bigl(z'(t)\bigr)^{\alpha }\bigr)'+q(t)x^{\beta } \bigl(\sigma (t)\bigr)=0,\quad t\geq t_{0}, $$(r(t)(z′(t))α)′+q(t)xβ(σ(t))=0,t≥t0, where $z(t)=x(t)+p_{1}(t)x(\tau (t))+p_{2}(t)x(\lambda (t))$z(t)=x(t)+p1(t)x(τ(t))+p2(t)x(λ(t)) and α, β are ratios of two positive odd integers. Our results improve and complement some well-known results which were published recently in the literature. Two examples are given to illustrate the efficiency of our results.