bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical and physiological differences between synchronous and asynchronous low intensity handcycling during practice-based learning in able-bodied men
Authors: Kraaijenbrink Cassandra , Vegter Riemer J. K. , Hensen Alexander H. R. , Wagner Heiko , van der Woude Lucas H. V.
Published: February 2020

Background

Originally, the cranks of a handcycle were mounted with a 180° phase shift (asynchronous). However, as handcycling became more popular, the crank mode switched to a parallel mounting (synchronous) over the years. Differences between both modes have been investigated, however, not into great detail for propulsion technique or practice effects. Our aim is to compare both crank modes from a biomechanical and physiological perspective, hence considering force and power production as a cause of physiological outcome measures. This is done within a practice protocol, as it is expected that motor learning takes place in the early stages of handcycling in novices.

Methods

Twelve able-bodied male novices volunteered to take part. The experiment consisted of a pre-test, three practice sessions and a post-test, which was subsequently repeated for both crank modes in a counterbalanced manner. In each session the participants handcycled for 3 × 4 minutes on a leveled motorized treadmill at 1.94 m/s. Inbetween sessions were 2 days of rest. 3D forces, handlebar and crank angle were measured on the left hand side. Kinematic markers were placed on the handcycle to monitor the movement on the treadmill. Lastly, breath-by-breath spirometry combined with heart-rate were continuously measured. The effects of crank mode and practice-based learning were analyzed using a two way repeated measures ANOVA, with synchronous vs asynchronous and pre-test vs post-test as within-subject factors.

Results

In the pre-test, asynchronous handcycling was less efficient than synchronous handcycling in terms of physiological strain, force production and timing. At the post-test, the metabolic costs were comparable for both modes. The force production was, also after practice, more efficient in the synchronous mode. External power production, crank rotation velocity and the distance travelled back and forwards on the treadmill suggest that asynchronous handcycling is more constant throughout the cycle.

Conclusions

As the metabolic costs were reduced in the asynchronous mode, we would advise to include a practice period, when comparing both modes in scientific experiments. For handcycle users, we would currently advise a synchronous set-up for daily use, as the force production is more effective in the synchronous mode, even after practice.
Chemokine CXCL13 in serum, CSF and blood–CSF barrier function: evidence of compartment restriction
Authors: Pilz Georg , Sakic Irma , Wipfler Peter , Kraus Jörg , Haschke-Becher Elisabeth , Hitzl Wolfgang , Trinka Eugen , Harrer Andrea
Published: February 2020

Background and purpose

Elevation of the chemokine CXCL13 in CSF frequently occurs during active and acute CNS inflammatory processes and presumably is associated with B cell-related immune activation. Elevation levels, however, vary a lot and “leaking” of CXCL13 from blood across dysfunctional brain barriers is a possible source. The aim was to clarify the relation between CXCL13 concentrations in CSF, CXCL13 concentrations in serum and blood–CSF barrier (BCSFB) function for a correct interpretation of the intrathecal origin of CXCL13.

Methods

We retrospectively analyzed CXCL13 of banked CSF/serum samples (n = 69) selected from patient records and categorized the CSF CXCL13 elevations as CXCL13 negative (< 30 pg/ml), low (30–100 pg/ml), medium (101–250 pg/ml), or high (> 250 pg/ml). CXCL13 concentrations in CSF and serum and the corresponding CSF/serum CXCL13 quotients (Qcxcl13) were compared to CSF/serum albumin quotients (QAlb) as a measure for BCSFB function. The CXCL13 negative category included two subgroups with normal and dysfunctional BCSFB.

Results

Serum CXCL13 concentrations were similar across categories with median levels around 100 pg/ml but differed between individuals (29 to > 505 pg/ml). Despite clear evidence in serum, CXCL13 was detectable only at trace amounts (medians 3.5 and 7.5 pg/ml) in CSF of the two CXCL13 negative subgroups irrespective of a normal or pathological QAlb. Moreover, we found no association between CSF and serum CXCL13 levels or between QAlb and CSF CXCL13 levels in any of the CSF CXCL13-delineated categories. CXCL13 apparently does not “leak” from blood into CSF. This implies an intrathecal origin also for low CSF CXCL13 levels and a caveat for analyzing the Qcxcl13, because higher serum than CSF concentrations arithmetically depress the Qcxcl13 resulting in misleadingly low CSF/serum quotients.

Conclusion

We demonstrated that CXCL13 does not cross from blood into CSF, not even during severe BCSFB dysfunction. CSF CXCL13 elevations therefore most likely always are CNS-derived, which highlights their relevance as indicator of inflammatory CNS processes. We recommend data should not be corrected for BCSFB permeability (QAlb) and not to calculate CSF/serum quotients for CXCL13 as these may introduce error.
Aberrant expression of miR-214 is associated with obesity-induced insulin resistance as a biomarker and therapeutic
Authors: Cheng Fangxiao , Yuan Geheng , He Jiao , Shao Yimin , Zhang Junqing , Guo Xiaohui
Published: February 2020

Background

Insulin resistance (IR) in obesity is associated with the occurrence of metabolic and cardiovascular diseases. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR.

Methods

Serum expression of miR-214 in obese patients with or without IR was estimated by quantitative real-time-PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic value of miR-214 in the patients. Obesity-induced IR animal and cell models were constructed, and the therapeutic ability of miR-214 was explored.

Results

Serum expression of miR-214 was decreased in obese patients compared with the healthy controls, and the lowest expression was observed in the cases with IR. Downregulation of miR-214 was significantly correlated with the serum DPP4 levels and HOMA-IR of the patients upon IR conditions, and was demonstrated to perform diagnostic accuracy for distinguishing obese patients with IR from those without IR. In obesity-associated IR animal and cell models, the downregulation of miR-214 was also been detected. According to the measurement of glucose and insulin tolerance and glucose uptake abilities, we found that the overexpression of miR-214 could be used to alleviate IR in the IR models, especially when collaboratively used with DPP4 inhibitor vildagliptin.

Conclusion

All data revealed that miR-214, as a regulator of DPP4, is decreased in obese patients with IR and may serve as a diagnostic biomarker. The upregulation of miR-214 could improve IR in obese rats and adipocytes, indicating that miR-214 has the therapeutic potential for obesity and IR.
A small-scale fractionation pipeline for rapid analysis of seed mucilage characteristics
Authors: Cowley James M. , Herliana Lina , Neumann Kylie A. , Ciani Silvano , Cerne Virna , Burton Rachel A.
Published: February 2020

Background

Myxospermy is a process by which the external surfaces of seeds of many plant species produce mucilage—a polysaccharide-rich gel with numerous fundamental research and industrial applications. Due to its functional properties the mucilage can be difficult to remove from the seed and established methods for mucilage extraction are often incomplete, time-consuming and unnecessarily wasteful of precious seed stocks.

Results

Here we tested the efficacy of several established protocols for seed mucilage extraction and then downsized and adapted the most effective elements into a rapid, small-scale extraction and analysis pipeline. Within 4 h, three chemically- and functionally-distinct mucilage fractions were obtained from myxospermous seeds. These fractions were used to study natural variation and demonstrate structure–function links, to screen for known mucilage quality markers in a field trial, and to identify research and industry-relevant lines from a large mutant population.

Conclusion

The use of this pipeline allows rapid analysis of mucilage characteristics from diverse myxospermous germplasm which can contribute to fundamental research into mucilage production and properties, quality testing for industrial manufacturing, and progressing breeding efforts in myxospermous crops.
Three-dimensional meniscus allograft sizing—a study of 280 healthy menisci
Authors: Beeler Silvan , Jud Lukas , von Atzigen Marco , Sutter Reto , Fürnstahl Philipp , Fucentese Sandro F. , Vlachopoulos Lazaros
Published: February 2020

Background

Inaccurate meniscus allograft size is still an important problem of the currently used sizing methods. The purpose of this study was to evaluate a new three-dimensional (3D) meniscus-sizing method to increase the accuracy of the selected allografts.

Methods

3D triangular surface models were generated from 280 menisci based on 50 bilateral and 40 unilateral knee joint magnetic resonance imaging (MRI) scans. These models served as an imaginary meniscus allograft tissue bank. Meniscus sizing and allograft selection was simulated for all 50 bilateral knee joints by (1) the closest mean surface distance (MeSD) (3D-MRI sizing with contralateral meniscus), (2) the smallest meniscal width/length difference in MRI (2D-MRI sizing with contralateral meniscus), and (3) conventional radiography as proposed by Pollard (2D-radiograph (RX) sizing with ipsilateral tibia plateau). 3D shape and meniscal width, length, and height were compared between the original meniscus and the selected meniscus using the three sizing methods.

Results

Allograft selection by MeSD (3D MRI) was superior for all measurement parameters. In particular, the 3D shape was significantly improved (p < 0.001), while the mean differences in meniscal width, length, and height were only slightly better than the allograft selected by the other methods. Outliers were reduced by up to 55% (vs. 2D MRI) and 83% (vs. 2D RX) for the medial meniscus and 39% (vs. 2D MRI) and 56% (vs. 2D RX) for the lateral meniscus.

Conclusion

3D-MRI sizing by MeSD using the contralateral meniscus as a reconstruction template can significantly improve meniscus allograft selection. Sizing using conventional radiography should probably not be recommended.

Trial registration

Kantonale Ethikkommission Zürich had given the approval for the study (BASEC-No. 2018-00856).
Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD
Authors: Andrade Nadja S. , Ramic Melina , Esanov Rustam , Liu Wenjun , Rybin Mathew J. , Gaidosh Gabriel , Abdallah Abbas , Del’Olio Samuel , Huff Tyler C. , Chee Nancy T. , Anatha Sadhana , Gendron Tania F. , Wahlestedt Claes , Zhang Yanbin , Benatar Michael , Mueller Christian , Zeier Zane
Published: February 2020

Background

The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. The C9ORF72 expansion encodes five dipeptide repeat proteins (DPRs) that are produced through a non-canonical translation mechanism. Among the DPRs, proline-arginine (PR), glycine-arginine (GR), and glycine-alanine (GA) are the most neurotoxic and increase the frequency of DNA double strand breaks (DSBs). While the accumulation of these genotoxic lesions is increasingly recognized as a feature of disease, the mechanism(s) of DPR-mediated DNA damage are ill-defined and the effect of DPRs on the efficiency of each DNA DSB repair pathways has not been previously evaluated.

Methods and results

Using DNA DSB repair assays, we evaluated the efficiency of specific repair pathways, and found that PR, GR and GA decrease the efficiency of non-homologous end joining (NHEJ), single strand annealing (SSA), and microhomology-mediated end joining (MMEJ), but not homologous recombination (HR). We found that PR inhibits DNA DSB repair, in part, by binding to the nucleolar protein nucleophosmin (NPM1). Depletion of NPM1 inhibited NHEJ and SSA, suggesting that NPM1 loss-of-function in PR expressing cells leads to impediments of both non-homologous and homology-directed DNA DSB repair pathways. By deleting NPM1 sub-cellular localization signals, we found that PR binds NPM1 regardless of the cellular compartment to which NPM1 was directed. Deletion of the NPM1 acidic loop motif, known to engage other arginine-rich proteins, abrogated PR and NPM1 binding. Using confocal and super-resolution immunofluorescence microscopy, we found that levels of RAD52, a component of the SSA repair machinery, were significantly increased iPSC neurons relative to isogenic controls in which the C9ORF72 expansion had been deleted using CRISPR/Cas9 genome editing. Western analysis of post-mortem brain tissues confirmed that RAD52 immunoreactivity is significantly increased in C9ALS/FTD samples as compared to controls.

Conclusions

Collectively, we characterized the inhibitory effects of DPRs on key DNA DSB repair pathways, identified NPM1 as a facilitator of DNA repair that is inhibited by PR, and revealed deficits in homology-directed DNA DSB repair pathways as a novel feature of C9ORF72-related disease.
Author Correction: 547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates
Authors: Li Ming-Li , Wu Shi-Hao , Zhang Jin-Jin , Tian Hang-Yu , Shao Yong , Wang Zheng-Bo , Irwin David M. , Li Jia-Li , Hu Xin-Tian , Wu Dong-Dong
Published: February 2020

Following publication of the original paper [1], the authors reported an error in the affiliation of Xin-Tian Hu, who is also affiliated with “Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China”.
Effects of synbiotic supplementation on energy and macronutrients homeostasis and muscle wasting of critical care patients: study protocol and a review of previous studies
Authors: Seifi Najmeh , Safarian Mohammad , Nematy Mohsen , Rezvani Reza , Khadem-Rezaian Majid , Sedaghat Alireza
Published: February 2020

Background

An extreme and persistent dysbiosis occurs among critically ill patients, regardless of the heterogeneity of disease. Dysbiosis in critically ill patients may make them prone to hospital-acquired infections, sepsis, multi-organ failure (MOF), energy homeostasis disturbance, muscle wasting, and cachexia. Modulation of gut microbiota through synbiotics can be considered as a potential treatment for muscle wasting and macronutrient homeostasis disturbances.

Methods

This is a prospective, single-center, double-blind, parallel randomized controlled trial with the aim to evaluate the effects of synbiotic supplementation on energy and macronutrient homeostasis and muscle wasting in critically ill patients. A total of 40 hemodynamically stable, adult, critically ill patients who receive enteral nutrition via a nasogasteric tube (NGT) in the 24–48 h after admission to critical care will be included in this study. Eligible patients will be randomly assigned to receive Lactocare (ZistTakhmir) capsules 500 mg every 12 h or a placebo capsule, which contains only the sterile maize starch and is similar to synbiotic capsules for 14 days. The synbiotic and placebo capsules will be given through the nasogastric tube, separately from gavage, after feeding.

Discussion

Gut microbiota modulation through synbiotics is proposed to improve clinical prognosis and reduce infectious complications, ventilator dependency, and length of ICU stay by improving energy and macronutrient homeostasis and reducing muscle protein catabolism.

Trial registration

Iranian Registry of Clinical Trials, IRCT20190227042857N1. Registered on 17 March 2019.
Effect of community active case-finding strategies for detection of tuberculosis in Cambodia: study protocol for a pragmatic cluster randomized controlled trial
Authors: Teo Alvin Kuo Jing , Prem Kiesha , Evdokimov Konstantin , Ork Chetra , Eng Sothearith , Tuot Sovannary , Chry Monyrath , Mao Tan Eang , Hsu Li Yang , Yi Siyan
Published: February 2020

Background

Cambodia has made notable progress in the fight against tuberculosis (TB). However, these gains are impeded by a significant proportion of undiagnosed cases. To effectively reach people with TB, active case-finding (ACF) strategies have been adopted by countries affected by the epidemic, including Cambodia, alongside passive case finding (PCF). Despite increased efforts to improve case detection, approximately 40% of TB cases in Cambodia remained undiagnosed in 2018. In Cambodia, several community-based TB ACF modalities have been implemented, but their effectiveness has yet to be systematically assessed.

Methods

This pragmatic cluster randomized controlled trial will be conducted between December 2019 and June 2021. We will randomize eight operational districts (clusters) in seven provinces (Kampong Cham, Kampong Thom, Prey Veng, Thbong Khmum, Kampong Chhnang, Kandal, and Kampong Speu) to either the control group (PCF) or the intervention groups (ACF using a seed-and-recruit model, ACF targeting household and neighborhood contacts, and ACF targeting persons aged ≥ 55 years using mobile screening units). The primary endpoints will be TB case notification rates, additionality, and cumulative yield of TB cases. The secondary endpoints include treatment outcomes, the number needed to screen to find one TB case, and cost-effectiveness outcome measures. We will analyze the primary and secondary endpoints by intention to treat. We will compare cluster and individual-level characteristics using Student’s t test and hierarchical or mixed-effect models to estimate the ratio of these means. The incremental cost-effectiveness ratio per disability-adjusted life year averted will also be considered as a benchmark to determine whether the interventions are cost-effective.

Discussion

This study will build an evidence base to inform future scale-up, implementation, and sustainability of ACF strategies in Cambodia and other similar settings. Implementation of this study will also complement TB control strategies in Cambodia by conducting ACF in operational districts without active interventions to find TB cases currently. Those who are ill and might have TB will be promptly screened, diagnosed, and linked to care. Early diagnosis and treatment initiation will also benefit their community by interrupting transmission and prevent further infections. The experience gained from this project will inform future attempts in conducting pragmatic trials in low-resource settings.

Trial registration

ClinicalTrials.gov, NCT04094350. Registered on 18 September 2019.
New insights from the biogas microbiome by comprehensive genome-resolved metagenomics of nearly 1600 species originating from multiple anaerobic digesters
Authors: Campanaro Stefano , Treu Laura , Rodriguez-R Luis M. , Kovalovszki Adam , Ziels Ryan M. , Maus Irena , Zhu Xinyu , Kougias Panagiotis G. , Basile Arianna , Luo Gang , Schlüter Andreas , Konstantinidis Konstantinos T. , Angelidaki Irini
Published: February 2020

Background

Microorganisms in biogas reactors are essential for degradation of organic matter and methane production. However, a comprehensive genome-centric comparison, including relevant metadata for each sample, is still needed to identify the globally distributed biogas community members and serve as a reliable repository.

Results

Here, 134 publicly available metagenomes derived from different biogas reactors were used to recover 1635 metagenome-assembled genomes (MAGs) representing different biogas bacterial and archaeal species. All genomes were estimated to be > 50% complete and nearly half ≥ 90% complete with ≤ 5% contamination. In most samples, specialized microbial communities were established, while only a few taxa were widespread among the different reactor systems. Metabolic reconstruction of the MAGs enabled the prediction of functional traits related to biomass degradation and methane production from waste biomass. An extensive evaluation of the replication index provided an estimation of the growth dynamics for microbes involved in different steps of the food chain.

Conclusions

The outcome of this study highlights a high flexibility of the biogas microbiome, allowing it to modify its composition and to adapt to the environmental conditions, including temperatures and a wide range of substrates. Our findings enhance our mechanistic understanding of the AD microbiome and substantially extend the existing repository of genomes. The established database represents a relevant resource for future studies related to this engineered ecosystem.
Molecular characterization of a Trichinella spiralis elastase-1 and its potential as a diagnostic antigen for trichinellosis
Authors: Hu Chen Xi , Jiang Peng , Yue Xin , Zeng Jie , Zhang Xin Zhuo , Song Yan Yan , Liu Ruo Dan , Zhang Xi , Wang Zhong Quan , Cui Jing
Published: February 2020

Background

Trichinella spiralis muscle larval (ML) excretion/secretion (ES) antigen is the most widely used diagnostic antigen of trichinellosis, but preparation of ES antigen requires collecting worms from infected animals, and detection of specific IgG against ML ES antigen may result in a false negative at the early stage of infection. The aim of the study was to characterize T. spiralis elastase-1 (TsEla) and to evaluate its potential as diagnostic antigen for trichinellosis.

Methods

The complete cDNA sequences of the TsEla gene were cloned and expressed, and recombinant (rTsEla) was purified. TsEla transcription and expression in different T. spiralis life-cycle stages was investigated by qPCR and western blotting, and its location in the nematodes was evaluated using an immunofluorescence assay (IFA). The antigenicity of rTsEla was investigated by western blotting analysis and ELISA. Anti-Trichinella IgG, IgM and IgE of experimentally infected mice and specific IgG antibodies of trichinellosis patients were assayed by rTsEla-ELISA and ES-ELISA.

Results

The results of the qPCR and western blotting showed that TsEla was expressed in various T. spiralis life stages. Natural TsEla was detected in the soluble proteins and ES proteins of different life stages. IFA revealed that TsEla was identified in the whole nematodes of various stages, especially in the cuticle, stichosome and genital primordium of the parasite. Serum anti-Trichinella IgM, IgG and IgE in infected mice was first detected by rTsEla-ELISA at 6, 10 and 12 days post-infection (dpi), and reached 100% at 8, 14 and 14 dpi, respectively. When rTsEla-ELISA and ES-ELISA were used to detect anti-Trichinella IgG in sera of trichinellosis patients, the sensitivity was 97.37% (37/38) and 89.74% (34/38) (P > 0.05), and the specificity was 99.10% (220/222) and 98.20% (218/222), respectively (P > 0.05). The rTsEla cross-reacted with only one serum sample out of 20 samples from paragonimiasis patients and 7 samples from clonorchiasis patients.

Conclusions

rTsEla is valuable to early diagnosis of trichinellosis and could be an alternative diagnostic antigen to the ML ES antigens.
Seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome
Authors: Duret Pierre-Marie , Meyer Nicolas , Saraux Alain , Devauchelle-Pensec Valérie , Seror Raphaele , Le-Guern Véronique , Larroche Claire , Perdriger Aleth , Sibilia Jean , Guardiolle Vianney , Mariette Xavier , Gottenberg Jacques-Eric
Published: February 2020

Background

To assess the presence of a seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome (pSS).

Methods

Data (date; visual analogue scales (VAS) for pain, fatigue and dryness) were extracted from three randomised placebo-controlled trials (RCTs) evaluating infliximab (TRIPSS; n = 103 patients), hydroxychloroquine (JOQUER; n = 120 patients) and rituximab (TEARS; n = 120 patients) and from the 5-year follow-up of the ASSESS prospective cohort (n = 395 patients). Data were analysed at each visit for each patient, according to the day, the month of the year and the season. Linear mixed models were used to take into account the repeated structure of the data and to analyse a potential cyclic effect.

Results

A total of 744, 584, 848 and 682 pain, fatigue and dryness VASs were collected on 632 subjects in spring, summer, fall and winter, respectively. No significant difference was observed in pain, fatigue and dryness, according to the month of the year or the season (all p values > 0.05).

Conclusion

In pSS, seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.
covRNA: discovering covariate associations in large-scale gene expression data
Authors: Urban Lara , Remmele Christian W. , Dittrich Marcus , Schwarz Roland F. , Müller Tobias
Published: February 2020

Objective

The biological interpretation of gene expression measurements is a challenging task. While ordination methods are routinely used to identify clusters of samples or co-expressed genes, these methods do not take sample or gene annotations into account. We aim to provide a tool that allows users of all backgrounds to assess and visualize the intrinsic correlation structure of complex annotated gene expression data and discover the covariates that jointly affect expression patterns.

Results

The Bioconductor package covRNA provides a convenient and fast interface for testing and visualizing complex relationships between sample and gene covariates mediated by gene expression data in an entirely unsupervised setting. The relationships between sample and gene covariates are tested by statistical permutation tests and visualized by ordination. The methods are inspired by the fourthcorner and RLQ analyses used in ecological research for the analysis of species abundance data, that we modified to make them suitable for the distributional characteristics of both, RNA-Seq read counts and microarray intensities, and to provide a high-performance parallelized implementation for the analysis of large-scale gene expression data on multi-core computational systems. CovRNA provides additional modules for unsupervised gene filtering and plotting functions to ensure a smooth and coherent analysis workflow.
Management of psoriasis-like rash associated with idelalisib monotherapy in a patient with refractory follicular lymphoma: a case report
Authors: Machan Salma , Plaza Carlos , Pérez-González Yosmar , Rodriguez-Pinilla Maria , Requena Luis , Cordoba Raul
Published: February 2020

Background

Follicular lymphoma is an indolent non-Hodgkin lymphoma that is most commonly diagnosed in elderly individuals. The majority of patients with follicular lymphoma present with advanced disease. Despite the recent advances in treatment, there remains a substantial unmet need for effective treatments for patients with relapsed/refractory follicular lymphoma. The PI3Kδ inhibitor idelalisib was approved by the European Medicines Agency in 2014 as a monotherapy for the treatment of adult patients with follicular lymphoma that is refractory to two prior lines of treatment. Real-world evidence from patients with follicular lymphoma treated with idelalisib indicates its utility in these patients.

Case presentation

This case report describes an 82-year-old, retired, white, female patient with refractory follicular lymphoma who achieved a partial response with idelalisib treatment. Despite experiencing two incidences of a psoriasis-like rash during idelalisib treatment that required effective management with topical steroids, the patient was able to restart treatment successfully and maintain a continued partial response.

Conclusions

The clinical relevance of the effective management of adverse events in this case demonstrates the opportunity to enable patients to remain on therapy, thereby maintaining long-term response and improving overall outcomes.
Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
Authors: Guan Siao-Syun , Wu Cheng-Tien , Liao Tse-Zung , Luo Tsai-Yueh , Lin Kun-Liang , Liu Shing-Hwa
Published: February 2020

Background

Cancer stem cells (CSCs) are involved in drug resistance, metastasis, and relapse of cancers, which can significantly affect tumor therapy. Hence, to develop specifically therapeutic target probe at CSCs for improvement of survival and quality of life of cancer patients is urgently needed. The CD166 protein has been suggested to be involved in colorectal cancer (CRC) tumorigenesis and to be considered a marker for colorectal CSCs (CRCSCs) detection. In this study, therefore, we attend to apply a nuclear imaging agent probe, Glycine18-Cystine-linked CD166-targeted peptides (CD166tp-G18C), to detect the changes of CD166 level in a CRC xenograft mouse model.

Results

We isolated the CD166-positive cells from the HCT15 CRC cell line (CD166+HCT15) and evaluated their morphology and ability of clone formation, migration, protein expression, and drug resistance. The CD166-positive HCT15 cells display the CSCs characteristics. We discovered and designed a CD166-targeted peptide (CD166tp-G18C) as a targeted probe of CRC stem-like cell for cell binding assay. The CD166tp-G18C confirmed the CD166 protein targeting ability in CD166+HCT15 cells. The diethylenetriaminopentaacetic acid (DTPA)-conjugated CD166tp-G18C further was labeled with indium-111 (111In-DTPA-CD166tp-G18C) as nuclear imaging agent for imaging and bio-distribution analysis in vivo. Finally, we observed that the111In-DTPA-CD166tp-G18C was significantly enhanced in tumor tissues of CD166+HCT15 xenograft mice as compared to the non-CD166tp-G18C control.

Conclusions

Our results indicated that the indium-111-labeled CD166tp-G18C may be served as a powerful tool for colorectal CSCs nuclear imaging in the CRC patients.
Adaptive filtering and analysis of EEG signals in the time-frequency domain based on the local entropy
Authors: Madhale Jadav Guruprasad , Lerga Jonatan , Štajduhar Ivan
Published: February 2020

The brain dynamics in the electroencephalogram (EEG) data are often challenging to interpret, specially when the signal is a combination of desired brain dynamics and noise. Thus, in an EEG signal, anything other than the desired electrical activity, which is produced due to coordinated electrochemical process, can be considered as unwanted or noise. To make brain dynamics more analyzable, it is necessary to remove noise in the temporal location of interest, as well as to denoise data from a specific spatial location. In this paper, we propose a novel method for noisy EEG analysis with accompanying toolbox which includes adaptive, data-driven noise removal technique based on the improved intersection of confidence interval (ICI)-based algorithm. Next, a local entropy-based method for EEG data analysis was designed and included in the toolbox. As shown in the paper, the relative intersection of confidence interval (RICI) procedure retains the dominant dipole activity projected on electrodes, while the local (short-term) Rényi entropy-based analysis of the EEG representation in the time-frequency domain is efficient in detecting the presence of P300 event-related potential (ERP) at specific electrodes. Namely, the P300 are detected as sharp drop of entropy in the temporal domain that enabled accurate calculation of the index of the noise class for the EEG signals.
Existence of extremal solutions for discontinuous Stieltjes differential equations
Authors: López Pouso Rodrigo , Márquez Albés Ignacio
Published: February 2020

Stieltjes differential equations, which contain equations with impulses and equations on time scales as particular cases, simply consist in replacing usual derivatives by derivatives with respect to a nondecreasing function. In this paper we prove new results for the existence of extremal solutions for discontinuous Stieltjes differential equations. In particular, we prove that the pointwise infimum of upper solutions of a Stieltjes differential equation is the minimal solution under certain hypotheses. These results can be adapted to the context of both difference equations and impulsive differential equations.
Global exponential stability of delayed inertial competitive neural networks
Authors: Shi Min , Guo Juan , Fang Xianwen , Huang Chuangxia
Published: February 2020

In this paper, the exponential stability for a class of delayed competitive neural networks is studied. By applying the inequality technique and non-reduced-order approach, some novel and useful criteria of global exponential stability for the addressed network model are established. Moreover, a numerical example is presented to show the feasibility and effectiveness of the theoretical results.
Dynamic correlation pattern amongst alternative energy market for diversification opportunities
Authors: Rehman Mobeen Ur
Published: February 2020

Last couple of decades witnessed recognition of energy markets as investment commodities which led interest of the international investment community. We investigate the potential of globally diverse alternative energy markets for optimal returns by analysing their correlation pattern. Our study employs daily data spanning from January 2006 to December 2017. To estimate pair-wise return co-movement, we employ rolling window multiple wavelet correlation based on decomposed returns using maximal overlap discrete wavelet transformation to infer implications for both short- and long-run investors. We witness maximum diversification between developed (World, Developed, EU, G7) and emerging (BRIC, Emerging) markets. Most of these combinations exhibit no traces of contagion during the financially and economically turbulent periods. Finally, we use non-linear causality test to highlight increased integration between our sampled alternative energy indices after financial and economic crises periods. Our results carry implications for short- and long-run investors as well as for policy makers.
Applying micro-computed tomography (micro-CT) and Raman spectroscopy for non-invasive characterization of coating and coating pigments on ancient Chinese papers
Authors: Li Tao , Liu Chuang , Wang Dongmei
Published: February 2020

The coating technique, supposedly invented by Chinese papermakers no later than the 3rd century AD, greatly improved paper sheets’ qualities of color, texture, writability, and printability. Alongside the dispersal of papermaking and surface-treatment techniques beyond China, coated papers were manufactured and used in many other regions of the world. Understanding the manufacture of coated papers, therefore, is crucial for perceiving how surface treatments were developed to meet the need for paper with enhanced properties. However, the characterization of coating and coating pigments on ancient Chinese papers has long remained an unsolved issue, and previous studies on this topic have often produced inconclusive results. To explore a non-invasive methodology that can more reliably characterize coated papers and the coating pigment on them, this article presents the results of a pilot study that applied micro-computed tomography (micro-CT) and Raman spectroscopy to samples of three Qing Dynasty (1644–1911 AD) papers and two handmade papers manufactured in China in the 1990s. Micro-CT revealed the coating layer(s) on Lajian (waxed coated paper) and Lengjinjian (gold-dusted paper) of the Qing Dynasty and characterized the modern raw xuan and bamboo papers as uncoated. Raman spectroscopy, together with handheld X-ray fluorescence analysis, identified the mineral-based pigment in the coating layer, suggesting the use of lead white or kaolin as the coating pigment. Additionally, Raman analysis confirmed the use of other mineral pigments (red lead and cinnabar), beeswax, and organic dyes (gamboge, kermesic acid, and possibly purpurin) in the manufacture of Lajian and Lengjinjian papers. The combination of micro-CT and Raman spectroscopy, it is therefore suggested, is a practical, more reliable approach for non-invasive investigation of coating and coating pigments on ancient Chinese paper specimens.
Non-contact visual control of personalized hand prostheses/exoskeletons by tracking using augmented reality glasses
Authors: Hazubski Simon , Hoppe Harald , Otte Andreas
Published: February 2020

A new concept for robust non-invasive optical activation of motorized hand prostheses by simple and non-contact commands is presented. In addition, a novel approach for aiding hand amputees is shown, outlining significant progress in thinking worth testing. In this, personalized 3D-printed artificial flexible hands are combined with commercially available motorized exoskeletons, as they are used e.g. in tetraplegics.
The prevalence, characteristics and outcome of seizure in tuberculous meningitis
Authors: Abdulaziz Ammar Taha Abdullah , Li Jinmei , Zhou Dong
Published: February 2020

Seizures are a common finding in patients with tuberculous meningitis (TBM), and associate with four times increased risk of death and neurological disability, especially in children. It has been reported that brain inflammation, diffuse neuronal injury, and reactive gliosis may all contribute to the pathogenesis of seizures in TBM. Early seizure onset may be associated with meningeal irritation and cerebral oedema; while, the late seizures are usually due to infarction, hydrocephalus, tuberculoma and paradoxical response. Moreover, recurrent uncontrolled seizures can evolve to status epileptics resulting in an increased risk of chronic epilepsy and poor prognosis. Therefore, this review aimed to assess the frequency of seizures in patients with TBM, and discuss the etiologies, mechanisms, and characteristics of seizures in TBM. Besides, we have searched the literature to identify the prognostic factors for chronic epilepsy after TBM.
Police involvement, characteristics and outcomes of place of safety referrals in the Scottish Highlands
Authors: Simpson Struan , Eze Jude
Published: February 2020

Aims and method

To characterise police involvement with those detained under place of safety legislation and determine factors associated with admission to hospital. Place of safety referrals over a 1-year period were identified retrospectively and evaluated.

Results

Place of safety legislation is generally used with regard to concerns about suicide. Individuals are often removed from high-risk areas and referrals to police are frequently initiated by individuals themselves. A diagnosis of mental illness or personality disorder predicted hospital admission. Presence of senior nursing staff at assessment, but not the seniority of the doctor, was associated with discharge.

Clinical implications

Closer multiagency working is required as police are currently being recruited to fill a void between mental health services and the population they serve. Junior doctors require more senior support in making complex, and often risky, emergency management decisions with this population.
Reviewing the burden of comorbidity in patients receiving specialist in-patient treatment for drug and alcohol problems
Authors: Bradley Alice , Martin Amy
Published: February 2020

Aims and method

To compare and contrast the burden of comorbidity in a population receiving in-patient treatment for substance misuse with that of a cohort admitted to the same unit 4 years previously. The Charlson Comorbidity Index (CCI) was used to quantify patients' comorbidity and predict 10-year survival.

Results

There was a marked reduction in predicted 10-year survival: in 2014, 22% of patients had a predicted 98% chance of 10-year survival, whereas only 2% in the 2018 cohort had a predicted 98% chance. Additionally, in 2014 only 9% of patients had a <20% 10-year predicted survival chance, whereas 28% in 2018 had a predicted 10-year survival chance of <20%. In this time, funding for services was cut by 23% and the 12-bed unit was reduced to 8 beds. This resulted in an increase in the average waiting time from 30 to 65 days. In 2018, more patients were admitted for alcohol detoxification, rising from 79% to 93% of admissions. Chronic respiratory disease remains the most prominent comorbidity; however, there is also an increase in the percentage of patients with liver disease.

Clinical implications

In-patient substance misuse units are known to serve individuals with complex illnesses. With service funding cuts, subsequent bed reductions and increased waiting times, this complexity is increasing, with a considerably higher burden of comorbidity. The consequential increased mortality risk highlights the ongoing need for adequate community and in-patient services with integrated care of mental and physical health alongside social work.
DNA damage response pathway alterations and clinical outcome in leiomyosarcoma.
Authors: Rosenbaum Evan , Jonsson Philip , Seier Kenneth , Chi Ping , Dickson Mark Andrew , Gounder Mrinal M. , Kelly Ciara Marie , Keohan Mary Louise , Qin Li-Xuan , Hensley Martee Leigh , D'Angelo Sandra P. , Tap William D.
Published: February 2020

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Background: Leiomyosarcoma (LMS) is a complex karyotype sarcoma with frequent alterations in the homologous recombination (HR) pathway. Genomically unstable tumors with DNA damage repair (DDR) deficiencies may have improved responses to DNA damaging therapies, such as cytotoxic chemotherapy or PARP inhibitors. Methods: We retrospectively reviewed LMS patients treated at MSKCC who had targeted somatic DNA sequencing (MSK-IMPACT) performed on tumor tissue. 33 DDR genes, including 16 HR genes, were analyzed for oncogenic alterations. A composite HR deficiency (HRD) score measured tumor genomic scarring for each patient. To determine if DDR alteration status is prognostic of outcome, we analyzed the recurrence-free survival (RFS) of patients who underwent complete resection, and the overall survival (OS) of the whole cohort. Results: 211 patients had IMPACT testing between March 2014 and October 2018; 48% of samples were primary tumors and 52% recurrent/metastatic sites. Among soft tissue LMS (stLMS), there were 35 men and 55 women. 20% of patients had an oncogenic DDR gene alteration, 72% of which were in the HR pathway (table below). Uterine LMS (uLMS) had more DDR alterations than stLMS, though not statistically significant (p = 0.084). BRCA2 (n = 14 cases), RAD51B (8), and ERCC5 (4) were most frequently altered. HRD score significantly correlated with HRD alteration status (p = 0.004). DDR or HRD altered status and HRD score were associated with shorter RFS in patients with resectable disease, independent of age (p < 0.05). Median OS for the cohort was 75 months (95% CI: 64 – 84). Men with stLMS had shorter OS compared to women (p = 0.025). OS did not significantly differ based on DDR or HRD status (p > 0.05). Conclusions: One-fifth of LMS patients have one or more oncogenic somatic alterations in the DDR pathway, predominantly in effectors of HR. DDR status may be prognostic of recurrence risk. Further analyses to determine the association between DDR status and response to cytotoxic chemotherapy are ongoing. [Table: see text]
Cancer-Related Distress: Revisiting the Utility of the National Comprehensive Cancer Network Distress Thermometer Problem List in Women With Gynecologic Cancers
Authors: Jewett Patricia I. , Teoh Deanna , Petzel Sue , Lee Heewon , Messelt Audrey , Kendall Jeffrey , Hatsukami Dorothy , Everson-Rose Susan A. , Blaes Anne H. , Vogel Rachel I.
Published: February 2020

PURPOSE:

The Distress Thermometer (DT) includes a measure of cancer-related distress and a list of self-reported problems. This study evaluated the utility of the DT problem list in identifying concerns most associated with distress and poorer quality of life (QOL) in survivors of gynecologic cancer.

METHODS:

Demographic, clinical, psychosocial functioning, and DT data were described among 355 women participating in a gynecologic cancer cohort. Problems from the DT list were ranked by prevalence, distress, and QOL. Logistic regression models explored factors associated with problems that were common (≥ 25% prevalence) and associated with distress and QOL.

RESULTS:

The average age of participants was 59.9 years (standard deviation [SD], 10.8 years). Most participants were non-Hispanic white (97%) and had ovarian (44%) or uterine (42%) cancer. The mean DT score was 2.7 (SD, 2.7); participants reported a mean of 7.3 problems (SD, 5.9 problems). The most common problems were fatigue (53.6%), worry (49.9%), and tingling (46.3%); least common problems were childcare (2.1%), fevers (2.1%), and substance abuse (1.1%). Report of some common problems, including tingling, sleep, memory, skin issues, and appearance, was not associated with large differences in distress or QOL. In contrast, some rarer problems such as childcare, treatment decisions, eating, housing, nausea, and bathing/dressing were associated with worse distress or QOL. Younger age, lower income, and chemotherapy were risk factors across common problems that were associated with worse distress or QOL (fatigue, nervousness, sadness, fears, and pain).

CONCLUSION:

The DT problem list did not easily identify concerns most associated with distress and low QOL in patients with gynecologic cancer. Adaptations that enable patients to report their most distressing concerns would enhance clinical utility of this commonly used tool.
Expression of E93 provides an instructive cue to control dynamic enhancer activity and chromatin accessibility during development
Authors: Nystrom Spencer L. , Niederhuber Matthew J. , McKay Daniel J.
Published: February 2020

How temporal cues combine with spatial inputs to control gene expression during development is poorly understood. Here, we test the hypothesis that the Drosophila transcription factor E93 controls temporal gene expression by regulating chromatin accessibility. Precocious expression of E93 early in wing development reveals that it can simultaneously activate and deactivate different target enhancers. Notably, the precocious patterns of enhancer activity resemble the wild-type patterns that occur later in development, suggesting that expression of E93 alters the competence of enhancers to respond to spatial cues. Genomic profiling reveals that precocious E93 expression is sufficient to regulate chromatin accessibility at a subset of its targets. These accessibility changes mimic those that normally occur later in development, indicating that precocious E93 accelerates the wild-type developmental program. Further, we find that target enhancers that do not respond to precocious E93 in early wings become responsive after a developmental transition, suggesting that parallel temporal pathways work alongside E93. These findings support a model wherein E93 expression functions as an instructive cue that defines a broad window of developmental time through control of chromatin accessibility.