bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPKα1 deletion in myofibroblasts exacerbates post-myocardial infarction fibrosis by a connexin 43 mechanism
Authors: Dufeys Cécile , Daskalopoulos Evangelos-Panagiotis , Castanares-Zapatero Diego , Conway Simon J. , Ginion Audrey , Bouzin Caroline , Ambroise Jérôme , Bearzatto Bertrand , Gala Jean-Luc , Heymans Stephane , Papageorgiou Anna-Pia , Vinckier Stefan , Cumps Julien , Balligand Jean-Luc , Vanhaverbeke Maarten , Sinnaeve Peter , Janssens Stefan , Bertrand Luc , Beauloye Christophe , Horman Sandrine 
Published: February 2021

AbstractWe have previously demonstrated that systemic AMP-activated protein kinase α1 (AMPKα1) invalidation enhanced adverse LV remodelling by increasing fibroblast proliferation, while myodifferentiation and scar maturation were impaired. We thus hypothesised that fibroblastic AMPKα1 was a key signalling element in regulating fibrosis in the infarcted myocardium and an attractive target for therapeutic intervention. The present study investigates the effects of myofibroblast (MF)-specific deletion of AMPKα1 on left ventricular (LV) adaptation following myocardial infarction (MI), and the underlying molecular mechanisms. MF-restricted AMPKα1 conditional knockout (cKO) mice were subjected to permanent ligation of the left anterior descending coronary artery. cKO hearts exhibit exacerbated post-MI adverse LV remodelling and are characterised by exaggerated fibrotic response, compared to wild-type (WT) hearts. Cardiac fibroblast proliferation and MF content significantly increase in cKO infarcted hearts, coincident with a significant reduction of connexin 43 (Cx43) expression in MFs. Mechanistically, AMPKα1 influences Cx43 expression by both a transcriptional and a post-transcriptional mechanism involving miR-125b-5p. Collectively, our data demonstrate that MF-AMPKα1 functions as a master regulator of cardiac fibrosis and remodelling and might constitute a novel potential target for pharmacological anti-fibrotic applications.
Free will and neurosurgical resections of the supplementary motor area: a critical review
Authors: Sjöberg Rickard L 
Published: February 2021

AbstractBackgroundResearch suggests that unconscious activity in the supplementary motor area (SMA) precedes not only certain simple motor actions but also the point at which we become aware of our intention to perform such actions. The extent to which these findings have implications for our understanding of the concepts of free will and personal responsibility has been subject of intense debate during the latest four decades.MethodsThis research is discussed in relation to effects of neurosurgical removal of the SMA in a narrative review.ResultsRemoval of the SMA typically causes a transient inability to perform non-stimulus-driven, voluntary actions. This condition, known as the SMA syndrome, does not appear to be associated with a loss of sense of volition but with a profound disruption of executive function/cognitive control.ConclusionsThe role of the SMA may be to serve as a gateway between the corticospinal tract and systems for executive function. Such systems are typically seen as tools for conscious decisions. What is known about effects of SMA resections would thus seem to suggest a view that is compatible with concepts of personal responsibility. However, the philosophical question whether free will exists cannot be definitely resolved on the basis of these observations.
Adolescents’ mental health problems increase after parental divorce, not before, and persist until adulthood: a longitudinal TRAILS study
Authors: Tullius Janne M. , De Kroon Marlou L. A. , Almansa Josué , Reijneveld Sijmen A. 
Published: February 2021

AbstractParental divorce is one of the most stressful life events for youth and is often associated with (long-lasting) emotional and behavioral problems (EBP). However, not much is known about the timing of the emergence of these EBP in adolescents relative to the moment of parental divorce, and its longitudinal effects. We therefore assessed this timing of EBP in adolescents of divorce and its longitudinal effects. We used the first four waves of the TRacking Adolescent’s Individual Lives Survey (TRAILS) cohort, which included 2230 10–12 years olds at baseline. EBP were measured through the Youth Self-Report (YSR), as internalizing and externalizing problems. We applied multilevel analysis to assess the effect of divorce on EBP. The levels of both internalizing and externalizing problems were significantly higher in the period after parental divorce (β = 0.03, and 0.03, respectively; p < 0.05), but not in the period before divorce, with a persistent and increasing effect over the follow-up periods compared to adolescents not experiencing divorce. Adolescents tend to develop more EBP in the period after parental divorce, not before. These effects are long-lasting and underline the need for better care for children with divorcing parents.
Which health-related reasons lead to prehospital emergency care and how does subjective emergency status connect to subsequent care?
Authors: Piedmont Silke , Reinhold Anna Katharina , Bock Jens-Oliver , Swart Enno , Robra Bernt-Peter 
Published: February 2021

Abstract
Objectives/Background
In many countries, the use of emergency medical services (EMS) increases steadily each year. At the same time, the percentage of life-threatening complaints decreases. To redesign the system, an assessment and consideration of the patients’ perspectives is helpful.

Methods
We conducted a paper-based survey of German EMS patients who had at least one case of prehospital emergency care in 2016. Four health insurance companies sent out the questionnaire to 1312 insured persons. We linked the self-reported data of 254 respondents to corresponding claims data provided by their health insurance companies. The analysis focuses a.) how strongly patients tend to call EMS for themselves and others given different health-related scenarios, b.) self-perceived health complaints in their own index case of prehospital emergency care and c.) subjective emergency status in combination with so-called “objective” characteristics of subsequent EMS and inpatient care. We report principal diagnoses of (1) respondents, (2) 57,240 EMS users who are not part of the survey and (3) all 20,063,689 inpatients in German hospitals. Diagnoses for group 1 and 2 only cover the inpatient stay that started on the day of the last EMS use in 2016.

Results
According to the survey, the threshold to call an ambulance is lower for someone else than for oneself. In 89% of all cases during their own EMS use, a third party called the ambulance. The most common, self-reported complaints were pain (38%), problems with heart and circulation (32%), and loss of consciousness (17%). The majority of respondents indicated that their EMS use was due to an emergency (89%). We could detect no or only weak associations between patients’ subjective urgency and different items for objective care.

Conclusion
Dispatchers can possibly optimize or reduce the disposition of EMS staff and vehicles if they spoke directly to the patients more often. Nonetheless, there is need for further research on how strongly the patients’ perceived urgency may affect the disposition, rapidness of the service and transport targets.
A biphasic multilayer computational model of human skin
Authors: Sachs David , Wahlsten Adam , Kozerke Sebastian , Restivo Gaetana , Mazza Edoardo 
Published: February 2021

AbstractThe present study investigates the layer-specific mechanical behavior of human skin. Motivated by skin’s histology, a biphasic model is proposed which differentiates between epidermis, papillary and reticular dermis, and hypodermis. Inverse analysis of ex vivo tensile and in vivo suction experiments yields mechanical parameters for each layer and predicts a stiff reticular dermis and successively softer papillary dermis, epidermis and hypodermis. Layer-specific analysis of simulations underlines the dominating role of the reticular dermis in tensile loading. Furthermore, it shows that the observed out-of-plane deflection in ex vivo tensile tests is a direct consequence of the layered structure of skin. In in vivo suction experiments, the softer upper layers strongly influence the mechanical response, whose dissipative part is determined by interstitial fluid redistribution within the tissue. Magnetic resonance imaging-based visualization of skin deformation in suction experiments confirms the deformation pattern predicted by the multilayer model, showing a consistent decrease in dermal thickness for large probe opening diameters.
Model and implementation of pseudorange-bias-free linear channel
Authors: Kou Yanhong , Wu Huiwen 
Published: February 2021

AbstractThe nonideal characteristics of the entire channel of satellite navigation signals from generation, propagation to reception will cause signal distortions, resulting in pseudorange biases. Such kind of biases cannot be eliminated by differential technologies and has become a core error source in high-accuracy applications. We study the theoretical model and implementation method of a pseudorange-bias-free linear channel. The ideal channel transfer function equation under the unbiased pseudorange requirement is first derived from the equivalent baseband model. Based on two corresponding criteria and the simulation of the influence of different amplitude- and phase-frequency responses, a digital phase compensation method based on an all-pass filter is proposed to eliminate pseudorange biases. Then the significant effects of the two phase equalizers are validated by a simulation example of the BPSK(10) signal. Finally, the real BDS3 PRN32 and PRN33 satellite B1C signals collected by a 40-m high-gain dish antenna are utilized to invert the channel transfer characteristics and processed by our software receiver. The measurement results demonstrate that the phase equalizers constructed according to either the linear phase criterion or the linear phase plus even-symmetric phase criterion can effectively reduce the pseudorange bias. The model and method provide a reference for payload and receiver optimization and are suitable for various signal structures and applications.
Organization of antibiotic stewardship in Europe: the way to go
Authors: Kern Winfried V. 
Published: February 2021

SummaryIt is more than two decades ago that a European Union conference on “The Microbial Threat” hosted by the Danish Government in Copenhagen in September 1998 issued recommendations to encourage good practice in the use of antimicrobial agents and reduce inappropriate prescribing. Essential components of those recommendations were antimicrobial teams in hospitals and the use of feedback to prescribers as well as educational activities. Two decades later, important surveillance systems on both antimicrobial resistance as well as on antibiotic consumption are functioning at the European level and in most European countries; European Committee on Antimicrobial Susceptibility Testing (EUCAST) has thoroughly re-evaluated, standardized and harmonized antibiotic susceptibility testing and breakpoints; there have been educational activities in many countries; and stewardship teams are now included in many guidelines and policy papers and recommendations. Yet, antimicrobial resistance problems in Europe have shifted from methicillin-resistant Staphylococus aureus (MRSA) to vancomycin-resistent Enterococcus faecium (VRE) and to multidrug-resistant gramnegative bacteria, while antibiotic consumption volumes, trends and patterns across countries do not show major and highly significant improvements. The way to go further is to recognize that better prescribing comes at a cost and requires investment in expert personnel, practice guideline drafting, and implementation aids, and, secondly, the setting of clear goals and quantitative targets for prescribing quality.
Agent‐based modeling of new product market diffusion: an overview of strengths and criticisms
Authors: Rand William , Stummer Christian 
Published: February 2021

AbstractMarket diffusion of new products is driven by the actions and reactions of consumers, distributors, competitors, and other stakeholders, all of whom can be heterogeneous in their individual characteristics, attitudes, needs, and objectives. These actors may also interact with others in various ways (e.g., through word of mouth or social influence). Thus, a typical consumer market constitutes a complex system whose behavior is difficult to foresee because stochastic impulses may give rise to complex emergent patterns of system reactions over time. Agent-based modeling, a relatively novel approach to understanding complex systems, is well equipped to deal with this complexity and, therefore, may serve as a valuable tool for both researchers studying particular market effects and practitioners seeking decision support for determining features of products under development or the appropriate combination of measures to accelerate product diffusion in a market. This paper provides an overview of the strengths and criticisms of such tools. It aims to encourage researchers in the field of innovation management, as well as practitioners, to consider agent-based modeling and simulation as a method for gaining deeper insights into market behavior and making better-informed decisions.
Better pain control with 8-gray single fraction palliative radiotherapy for skeletal metastases: a Bayesian network meta-analysis
Authors: Migliorini Filippo , Eschweiler Jörg , Trivellas Andromahi , Driessen Arne , Knobe Matthias , Tingart Markus , Maffulli Nicola 
Published: February 2021

AbstractExternal Beam Radiotherapy (EBRT) allows remarkable pain control in patients with skeletal metastases. We performed a Bayesian network meta-analysis comparing the most commonly used radiotherapy regimens for palliative management in patients with skeletal metastases. The main online databases were accessed in October 2020. All randomized clinical trials evaluating the irradiation of painful bone metastases were considered. The following irradiation patterns were analysed and included in the present network meta-analysis: 8 Gy- and 10 Gy/single fraction, 20 Gy/5 fractions, 30 Gy/10 fractions. The Bayesian hierarchical random-effect model analysis was adopted in all comparisons. The Log Odds-Ratio (LOR) statistical method for dichotomic data was adopted for analysis. Data from 3595 patients were analysed. The mean follow-up was 9.5 (1 to 28) months. The cumulative mean age was 63.3 ± 2.9. 40.61% (1461 of 3595 patients) were female. The 8Gy/single fraction protocol detected reduced rate of “no pain response” (LOR 3.39), greater rate of “pain response” (LOR-5.88) and complete pain remission (LOR-7.05) compared to the other dose patterns. The 8Gy group detected a lower rate of pathological fractures (LOR 1.16), spinal cord compression (LOR 1.31) and re-irradiation (LOR 2.97) compared to the other dose patterns. Palliative 8Gy/single fraction radiotherapy for skeletal metastases shows outstanding results in terms of pain control, re-irradiations, pathological fractures and spinal cord compression, with no differences in terms of survivorship compared to the other multiple dose patterns.Level of evidence: I, Bayesian network meta-analysis of RCTs.
Adult Attachment, Differentiation of Self, and Relationship Satisfaction in Lesbians and Gay Men
Authors: Sommantico Massimiliano , Iorio Ilaria , Lacatena Marina , Parrello Santa 
Published: February 2021

AbstractWe examined adult attachment styles, differentiation of self, and relationship satisfaction in a sample of 298 Italian lesbians (48%) and gay men (52%), all of whom were ages 19–71 years (M = 36.1; SD = 11.8) and in a couple relationship for at least six months. Participants were recruited via the Internet and completed a web-based survey. We tested the hypotheses that attachment insecurity and differentiation of self would predict relationship satisfaction, as well as that differentiation of self would mediate the relationship between adult attachment and relationship satisfaction. Results supported the hypotheses, thus indicating that attachment insecurity and differentiation of self were correlated with and predicted relationship satisfaction. Furthermore, results supported the hypothesized mediating role of differentiation of self. Finally, results indicated that younger participants, lesbians, and participants in civil unions reported higher levels of relationship satisfaction. Implications for counselors and therapists working with LG populations are discussed.
A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors
Authors: Yamamoto Noboru , Shimizu Toshio , Yonemori Kan , Kitano Shigehisa , Kondo Shunsuke , Iwasa Satoru , Koyama Takafumi , Sudo Kazuki , Sato Jun , Tamura Kenji , Tomomatsu Junichi , Ono Makiko , Fukuda Naoki , Takahashi Shunji 
Published: February 2021

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017
Evaluating macrophytes as indicators of anthropogenic pressures in rivers in Ireland
Authors: Bucior Adam , Rippey Brian , McElarney Yvonne , Douglas Richard 
Published: February 2021

AbstractThe ability of macrophytes to indicate pressures in rivers was assessed by comparing metrics for nitrate (NO3), ammonia (NH4), soluble reactive phosphorus (SRP), dissolved oxygen saturation (DO), pH (PH) and siltation (SUBS) with direct estimates of the pressures at 810 sites in the Republic of Ireland, supplemented with General Linear Models (GLMs). The bivariate and rank correlation coefficients using the full data range and the first and fourth quartiles of the river pressures varied between 0.22 and − 0.39 for NO3 and DO; they were smaller or not significant for the other four metrics. The GLMs provided evidence for an independent association between NO3 and the nitrate concentration and SUBS and ammonia, indicating some specificity for these metrics. Discriminating sites in the first and fourth quartiles produced Type II errors between 37 (PH) and 69% (NH4), with a mean of 50. As the pressure-impact relationships are not precise enough (low correlation coefficients) that evidence from a single macrophyte metric is reliable, combining the metric with evidence from other biological groups at one site or from three or more sites may be the most useful approach.
Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China
Authors: Yang Jiexia , Hou Yaping , Guo Fangfang , Peng Haishan , Wang Dongmei , Li Yi , OY Haoxin , Wang Yixia , Lu Jian , Yin Aihua 
Published: February 2021

Abstract
Background
Noninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). However, there is less information on the performance of NIPT in detecting SCAs.

Methods
A cohort of 47,800 pregnancies was recruited to review the high-risk NIPT results for SCAs. Cell-free fetal DNA (cffDNA) was extracted and sequenced. All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA).

Results
A total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. Prenatal diagnosis, including karyotyping analysis and CMA, was available in 170 cases. The positive predictive value (PPV) was 30.00% for 45,X, 70.58% for 47,XXX, and 81.13% for 47,XYY/47,XXY. In addition, 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study.

Conclusion
Our study showed that NIPT was reliable for screening SCAs based on a large sample, and it performed better in predicting sex chromosome trisomies than monosomy X. Our study will provide an important reference for clinical genetic counseling and further processing of the results.
The contemporary pulmonary artery catheter. Part 1: placement and waveform analysis
Authors: Bootsma I. T. , Boerma E. C. , de Lange F. , Scheeren T. W. L. 
Published: February 2021

AbstractNowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular (RV) performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using cold bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which at random heats up the blood. In this first part, the insertion techniques, interpretation of waveforms of the PAC, the interaction of waveforms with the respiratory cycle and airway pressure as well as pitfalls in waveform analysis are discussed. The second part will cover the measurements of the contemporary PAC including measurement of continuous cardiac output, RV ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements will be highlighted there as well. We conclude that thorough understanding of measurements obtained from the PAC are the first step in successful application of the PAC in daily clinical practice.