bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the HIV-Associated TB Epidemic and the Impact of Interventions Aimed at Epidemic Control
Authors: Dodd P. J. , Pretorius C. , Williams B. G. 
Published: December 2019

Abstract
In this chapter, we focus on mathematical models of tuberculosis epidemiology (TB) that include interactions with HIV and an explicit representation of transmission. We review the natural history of TB and illustrate how its features are simplified and incorporated in mathematical models. We then review the ways HIV influences the natural history of TB, the interventions that have been considered in models, and the way these individual-level effects are represented in models. We then go on to consider population-level effects, reviewing the TB/HIV modelling literature. We first review studies whose focus was on purely epidemiological modelling, and then studies whose focus was on modelling the impact of interventions. We conclude with a summary of the uses and achievements of TB/HIV modelling and some suggested future directions.
Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers
Authors: Arvidsson Michel , Dahl Marja-Liisa , Beck Olof , Ackehed Gerd , Nordin Karin , Rosenborg Staffan 
Published: December 2019

AbstractPurposeThe primary aim of this study was to explore the potential of alternative sampling matrices for methylphenidate by assessing the correlations betweendl-threo-methylphenidate anddl-threo-ritalinic acid concentrations in exhaled breath and oral fluid with those in plasma, in repeated samples collected after a single oral dose of methylphenidate. The secondary aim was to study the enantioselective pharmacokinetics of methylphenidate in plasma, with a focus on interindividual variability in the metabolism of methylphenidate to ritalinic acid.MethodsTwelve healthy volunteers received a single oral dose ofdl-threo-methylphenidate (Ritalin®capsules, 20 mg). Venous blood samples were collected for 24 h, and plasma analyzed forthreo-enantiomers of methylphenidate and ritalinic acid with LC-MS/MS. Repeated sampling of exhaled breath, using a particle filter device, and of non-stimulated oral fluid, using a felt pad device, was also performed. Exhaled breath and oral fluid were analyzed with a non-enantioselective LC-MS/MS method fordl-threo-methylphenidate anddl-threo-ritalinic acid.ResultsIn all subjects,d-threo-methylphenidate was detectable in plasma for at least 15 h after the dose with a biphasic profile.l-threo-Methylphenidate was measurable in only five subjects and in most cases in low concentrations. However, one female subject displayed a biphasic concentration-time profile forl-threo-methylphenidate. This subject also had the highestd-threo-methylphenidate AUC (191 ng*h/mL versus 32–119 ng*h/mL in the other subjects).d-threo-Ritalinic acid concentrations were on average 25-fold higher (range 6–126) than the correspondingd-threo-methylphenidate concentrations. Single-time point plasma concentration ratios betweend-threo-ritalinic acid andd-threo-methylphenidate 1.5–12 h after dose correlated highly (r= 0.88–0.98) with thed-threo-ritalinic acid AUC/d-threo-methylphenidate AUC ratio. In eleven subjects,dl-threo-methylphenidate in oral fluid mirrored the biphasic profile of methylphenidate (sum ofd-andl-threo-enantiomers) in plasma, but the concentrations in oral fluid were on average 1.8 times higher than in plasma.dl-threo-Methylphenidate was detected in exhaled breath in all subjects, but there was no consistent concentration-time pattern.ConclusionsIn some subjects, the pharmacologically less activel-threo-enantiomer may contribute to the total plasma methylphenidate concentrations. Monitoring methylphenidate concentrations without enantiomeric determination carries the risk of missing such subjects, which might affect how the plasma concentrations of methylphenidate are interpreted and used for clinical decision making. The use of exhaled breath and oral fluid to assess medication adherence to MPH in patients with ADHD warrants further studies.
Diffusion-weighted imaging of the breast—a consensus and mission statement from the EUSOBI International Breast Diffusion-Weighted Imaging working group
Authors:   On behalf of the EUSOBI international Breast Diffusion-Weighted Imaging working group, Baltzer Pascal , Mann Ritse M. , Iima Mami , Sigmund Eric E. , Clauser Paola , Gilbert Fiona J. , Martincich Laura , Partridge Savannah C. , Patterson Andrew , Pinker Katja , Thibault Fabienne , Camps-Herrero Julia , Le Bihan Denis 
Published: December 2019

Abstract
The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of b values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications.
Key Points
• The working group considers breast DWI an essential part of a multiparametric breast MRI protocol and encourages its use.
• Basic requirements for routine clinical application of breast DWI are provided, including recommendations on b values, fat saturation, spatial resolution, and other sequence parameters.
• Diffusion levels in breast lesions are defined based on meta-analysis data and methods to obtain a reliable ADC value are detailed.
Changes of trace element status during aging: results of the EPIC-Potsdam cohort study
Authors: Baudry Julia , Kopp Johannes F. , Boeing Heiner , Kipp Anna P. , Schwerdtle Tanja , Schulze Matthias B. 
Published: December 2019

Abstract
Purpose
We aimed to evaluate age-dependent changes of six trace elements (TE) [manganese (Mn), iron (Fe), zinc (Zn), copper (Cu), iodine (I), and selenium (Se)] over a 20-year period.

Methods
TE concentrations were determined using repeated serum samples taken at baseline and after 20 years of follow-up from 219 healthy participants of the EPIC-Potsdam study, using inductively coupled plasma tandem mass spectrometry. For each TE, absolute and relative differences were calculated between the two time points, as well as the proportion of individuals within normal reference ranges. Interdependence between age-related TE differences was investigated using principal component analysis (PCA). Relationships between selected factors (lifestyle, sociodemographic, anthropometric factors, and hypertension) and corresponding TE longitudinal variability were examined using multivariable linear regression models.

Results
Median age of our study sample was 58.32 years (4.42) at baseline and 40% were females. Median Mn, Zn, Se concentrations and Se to Cu ratio significantly decreased during aging while median Fe, Cu, I concentrations and Cu to Zn ratio significantly increased. A substantial percentage of the participants, at both time points, had Zn concentrations below the reference range. The first PCA-extracted factor reflected the correlated decline in both Mn and Zn over time while the second factor reflected the observed (on average) increase in both Cu and I over time. Overall, none of the investigated factors were strong determinants of TE longitudinal variability, except possibly dietary supplement use, and alcohol use for Fe.

Conclusions
In conclusion, in this population-based study of healthy elderly, decrease in Mn, Zn, and Se concentrations and increase in Fe, Cu, and I concentrations were observed over 20 years of follow-up. Further research is required to investigate dietary determinants and markers of TE status as well as the relationships between TE profiles and the risk of age-related diseases.
Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma
Authors: Xu Enhong , Liang Xiaoben , Ji Zhenhua , Zhao Shuwei , Li Li , Lang Juntian 
Published: December 2019

Abstract
Purpose
The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear.

Methods
Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell’s growth, proliferation, apoptosis, invasion and migration.

Results
MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells’ proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu).

Conclusion
In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.
Hospital volume and outcome in inguinal hernia repair: analysis of routine data of 133,449 patients
Authors: Maneck M. , Köckerling F. , Fahlenbrach C. , Heidecke C. D. , Heller G. , Meyer H. J. , Rolle U. , Schuler E. , Waibel B. , Jeschke E. , Günster C. 
Published: December 2019

Abstract
Introduction
Inguinal hernias are repaired using either open or minimally invasive surgical techniques. For both types of surgery it has been demonstrated that a higher annual surgeon volume is associated with a lower risk of recurrence. This present study investigated the volume-outcome implications for recurrence operations, surgical complications, rate of chronic pain requiring treatment, and 30-day mortality based on the hospital volume.

Materials and methods
The data basis used was the routine data collected throughout the Federal Republic of Germany for persons insured by the Local General Sickness Fund “AOK” who had undergone inpatient inguinal hernia repair between 2013 and 2015. Complications were recorded by means of indicators. Hospitals were divided into five groups on the basis of the annual caseload volume: 1–50, 51–75, 76–100, 101–125, and ≥ 126 inguinal hernia repairs per year. The effect of the hospital volume on the indicators was assessed using multiple logistic regression.

Results
133,449 inguinal hernia repairs were included. The incidence for recurrence operations was 0.95%, for surgical complications 4.22%, for chronic pain requiring treatment 2.87%, and for the 30-day mortality 0.28%. Low volume hospitals (1–50 and 51–75 inguinal hernia repairs per year) showed a significantly increased recurrence risk compared to high volume hospitals with ≥ 126 inguinal hernia repairs per year (odds ratio: 1.53 and 1.24). No significant correlations were found for the other results.

Conclusions
The study gives a detailed picture of hospital care for inguinal hernia repair in Germany. Furthermore, it was noted that the risk of hernia recurrence decreases in line with a rising caseload of the treating hospital.
Impact of thrombocytes, on bacterial growth and antimicrobial activity of selected antibiotics
Authors: Nussbaumer-Pröll Alina Karoline , Eberl Sabine , Reiter Birgit , Stimpfl Thomas , Jäger Walter , Poschner Stefan , Zeitlinger Markus 
Published: December 2019

AbstractIn vitro pharmacodynamic models are used to optimize in vivo dosing regimens in antimicrobial drug development. One limiting factor of such models is the lack of host factors such as corpuscular blood components as erythrocytes which have already been shown to impact activity of antibiotics and/or growth of the pathogen. However, the impact of thrombocytes has not previously been investigated. We set out to investigate if the addition of thrombocytes (set to physiological concentrations in blood of healthy human, i.e., 5 × 105 thrombocytes/μL standard growth media Mueller Hinton Broth, MHB) has an influence on bacterial growth and on the efficacy of antibiotics against Gram+ and Gram− bacteria. Growth assays and time-killing-curves (TKC) were performed with ATCC-strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa in triplicate over 24 h. The same approach was followed for 5 clinical isolates of Escherichia coli. Meropenem, ciprofloxacin, and tigecycline were tested as representatives of broad-spectrum antibiotics, and concentrations several-fold above and below the minimal inhibitory concentration (MIC) were simulated. No significant impact of thrombocytes was found on bacterial growth or antimicrobial stability for the investigated agents. Bacteria reduced thrombocyte content to different degree, indicating direct interaction of pathogens and thrombocytes. Impact on bacterial killing was observed but was not fully reproducible when thrombocytes from different donors where used. While interaction of bacteria and thrombocytes was evident in the present study, interaction between antibiotic activity and thrombocytes seems unlikely. Whether variability was caused by different thrombocyte concentrates needs further investigation.
Work functions shaping the ability to innovate: insights from the case of the safety engineer
Authors: Asplund Fredrik , Ulfvengren Pernilla 
Published: December 2019

AbstractTo perform as intended, firms are divided into work functions that contribute to the behaviour-shaping constraints under which individuals build their skills, knowledge and networks. These in turn provide a specialized perspective on organisational structure and culture. In a mixed methods study involving interviews and statistical analyses, we investigate whether a work function can thereby affect individuals’ innovation foci and efficacy. Safety engineers, central to firms developing Cyber-Physical Systems (CPS), are shown to play a significant role in identifying and supporting viable innovation related to organisational aspects. Results indicate that safety engineers could use the firm’s collaborative innovation process to facilitate organisational learning, helping different work functions come together to construct working practices aligned with the organisational values of the firm. This is explained by their understanding of safety culture—a specialized understanding of organisational culture and complexity provided by their work function. We conclude that work functions that provide their members with a perspective well aligned with their firm’s organisational values can instil the ability to identify and support organisational innovation. This suggests that safety engineers in CPS domains could be effective in a mediatory role, facilitating innovative changes to organisational structures and processes when introducing and operating safety management systems. Stronger aspects of organisational liaising and systems thinking could reinforce this ability—the former by a wider scope and motivation leading to an increased skill in communicating with dissimilar individuals, and the latter by providing the skills and tools needed to analyse the politics of complex organisations.
Human Auditory Detection and Discrimination Measured with the Pupil Dilation Response
Authors: Bala Avinash D. S. , Whitchurch Elizabeth A. , Takahashi Terry T. 
Published: December 2019

AbstractIn the standard Hughson-Westlake hearing tests (Carhart and Jerger 1959), patient responses like a button press, raised hand, or verbal response are used to assess detection of brief test signals such as tones of varying pitch and level. Because of its reliance on voluntary responses, Hughson-Westlake audiometry is not suitable for patients who cannot follow instructions reliably, such as pre-lingual infants (Northern and Downs 2002). As an alternative approach, we explored the use of the pupillary dilation response (PDR), a short-latency component of the orienting response evoked by novel stimuli, as an indicator of sound detection. The pupils of 31 adult participants (median age 24 years) were monitored with an infrared video camera during a standard hearing test in which they indicated by button press whether or not they heard narrowband noises centered at 1, 2, 4, and 8 kHz. Tests were conducted in a quiet, carpeted office. Pupil size was summed over the first 1750 ms after stimulus delivery, excluding later dilations linked to expenditure of cognitive effort (Kahneman and Beatty 1966; Kahneman et al. 1969). The PDR yielded thresholds comparable to the standard test at all center frequencies tested, suggesting that the PDR is as sensitive as traditional methods of assessing detection. We also tested the effects of repeating a stimulus on the habituation of the PDR. Results showed that habituation can be minimized by operating at near-threshold stimulus levels. At sound levels well above threshold, the PDR habituated but could be recovered by changing the frequency or sound level, suggesting that the PDR can also be used to test stimulus discrimination. Given these features, the PDR may be useful as an audiometric tool or as a means of assessing auditory discrimination in those who cannot produce a reliable voluntary response.
High-level expression of highly active and thermostable trehalase from Myceliophthora thermophila in Aspergillus niger by using the CRISPR/Cas9 tool and its application in ethanol fermentation
Authors: Dong Liangbo , Lin Xiaotong , Yu Dou , Huang Lianggang , Wang Bin , Pan Li 
Published: December 2019

Abstract
Trehalase catalyzes the hydrolysis of the non-reducing disaccharide trehalose. The highly active trehalase MthT from Myceliophthora thermophila was screened from the trehalase genes of six species of filamentous fungi. An ingenious multi-copy knock-in expression strategy mediated by the CRISPR/Cas9 tool and medium optimization were used to improve MthT production in Aspergillus niger, up to 1698.83 U/mL. The protein background was dramatically abated due to insertion. The recombinant MthT showed optimal activity at pH 5.5 and 60 °C, and exhibited prominent thermal stability between 50 and 60 °C under acid conditions (pH 4.5–6.5). The ethanol conversion rate (ethanol yield/total glucose) was significantly improved by addition of MthT (51.88%) compared with MthT absence (34.38%), using 30% starch saccharification liquid. The results of this study provided an effective strategy, established a convenient platform for heterologous expression in A. niger and showed a potential strategy to decrease production costs in industrial ethanol production.
Analysis and control of max-plus linear discrete-event systems: An introduction
Authors: De Schutter Bart , van den Boom Ton , Xu Jia , Farahani Samira S. 
Published: December 2019

AbstractThe objective of this paper is to provide a concise introduction to the max-plus algebra and to max-plus linear discrete-event systems. We present the basic concepts of the max-plus algebra and explain how it can be used to model a specific class of discrete-event systems with synchronization but no concurrency. Such systems are called max-plus linear discrete-event systems because they can be described by a model that is “linear” in the max-plus algebra. We discuss some key properties of the max-plus algebra and indicate how these properties can be used to analyze the behavior of max-plus linear discrete-event systems. Next, some control approaches for max-plus linear discrete-event systems, including residuation-based control and model predictive control, are presented briefly. Finally, we discuss some extensions of the max-plus algebra and of max-plus linear systems.
Risk of intellectual disability in children born appropriate-for-gestational-age at term or post-term: impact of birth weight for gestational age and gestational age
Authors: Chen Ruoqing , Tedroff Kristina , Villamor Eduardo , Lu Donghao , Cnattingius Sven 
Published: December 2019

AbstractChildren born small for gestational age have a higher risk of intellectual disability. We investigated associations of birth weight for gestational age percentile and gestational age with risk of intellectual disability in appropriate-for-gestational-age (AGA) children. We included 828,948 non-malformed term or post-term AGA singleton children (including 429,379 full siblings) born between 1998 and 2009 based on data from the Swedish Medical Birth Register. Diagnosis of intellectual disability after 3 years of age was identified through the Patient Register. Using Cox regression models, we calculated hazard ratios (HRs) with 95% confidence intervals (CIs) of intellectual disability among children with different birth weight percentiles and gestational age in the whole population and in a subpopulation of full siblings. A total of 1688 children were diagnosed with intellectual disability during follow-up. HRs (95% CIs) of intellectual disability for the low birth weight percentile groups (10th–24th and 25th–39th percentiles, respectively) versus the reference group (40th–59th percentiles) were 1.43 (1.22–1.67) and 1.28 (1.10–1.50) in population analysis and 1.52 (1.00–2.31) and 1.44 (1.00–2.09) in sibling comparison analysis. The increased risk for low birth weight percentiles in population analysis was stable irrespective of gestational age. A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, although not in sibling comparison analysis. These findings suggest that among AGA children born at term or post-term, lower birth weight percentiles within the normal range are associated with increased risk of intellectual disability, regardless of gestational age.