bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive activity of Vδ2+ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength
Authors: Schilbach Karin , Krickeberg Naomi , Kaißer Carlotta , Mingram Simon , Kind Janika , Siegers Gabrielle M. , Hashimoto Hisayoshi 
Published: January 2020

AbstractDespite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2+T cells with immunosuppressive function on autologous αβ T cells. We found that negatively freshly isolated Vδ2+T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, Vδ2+T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on αβ T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of Vδ2+T cells. This indicates that Vδ2+T cells’ suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. Vδ2+T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of Vδ2+T cells via the Vδ2 TCR for activation and expansion induces Vδ2+T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. Taken together, the study is a further step to understand—in more detail—the suppressive activity of Vδ2+γδ T cells.
ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease
Authors: Evans Charles E. , Miners James S. , Piva Giulia , Willis Christine L. , Heard David M. , Kidd Emma J. , Good Mark A. , Kehoe Patrick G. 
Published: January 2020

AbstractMid-life hypertension and cerebrovascular dysfunction are associated with increased risk of later life dementia, including Alzheimer’s disease (AD). The classical renin–angiotensin system (cRAS), a physiological regulator of blood pressure, functions independently within the brain and is overactive in AD. cRAS-targeting anti-hypertensive drugs are associated with reduced incidence of AD, delayed onset of cognitive decline, and reduced levels of Aβ and tau in both animal models and human pathological studies. cRAS activity is moderated by a downstream regulatory RAS pathway (rRAS), which is underactive in AD and is strongly associated with pathological hallmarks in human AD, and cognitive decline in animal models of CNS disease. We now show that enhancement of brain ACE2 activity, a major effector of rRAS, by intraperitoneal administration of diminazene aceturate (DIZE), an established activator of ACE2, lowered hippocampal Aβ and restored cognition in mid-aged (13–14-month-old) symptomatic Tg2576 mice. We confirmed that the protective effects of DIZE were directly mediated through ACE2 and were associated with reduced hippocampal soluble Aβ42 and IL1-β levels. DIZE restored hippocampal MasR levels in conjunction with increased NMDA NR2B and downstream ERK signalling expression in hippocampal synaptosomes from Tg2576 mice. Chronic (10 weeks) administration of DIZE to pre-symptomatic 9–10-month-old Tg2576 mice, and acute (10 days) treatment in cognitively impaired 12–13-month-old mice, prevented the development of cognitive impairment. Together these data demonstrate that ACE2 enhancement protects against and reverses amyloid-related hippocampal pathology and cognitive impairment in a preclinical model of AD.
Ramsay Hunt syndrome: characteristics and patient self-assessed long-term facial palsy outcome
Authors: Kanerva Mervi , Jones Sanna , Pitkaranta Anne 
Published: January 2020

AbstractPurposeTo explore the characteristics, medical treatments, and long-term facial palsy outcome in Ramsay Hunt syndrome.MethodsPatient questionnaire including self-assessment of long-term facial palsy outcome and retrospective chart review. Initial facial palsy grade was compared to self-assessed or patient record stated palsy outcome. Occurrence of different characteristics (blisters, hearing loss, vertigo, etc.) of the syndrome were assessed.ResultsAltogether 120 patients were included of which 81 answered the questionnaire. All but one patient had received virus medication (aciclovir, valaciclovir), and half received simultaneous corticosteroids. If the medication was started within 72 h of Ramsay Hunt diagnosis, facial palsy recovered totally or with only slight sequelae in over 80% of the patients. Only a minority of the patients experienced varicella blisters simultaneously with facial palsy, blisters more often preceded or followed the palsy. Approximately 20% of the patients had their blisters in hidden places in the ear canal or mouth.ConclusionsThe long-term outcome of facial palsy in medically treated Ramsay Hunt syndrome was approaching the outcome of Bell’s palsy. It is crucial to ask and inform the patient about the blisters and look for them since, more often than not, the blisters precede or follow the palsy and can be in areas not easily seen.
Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis
Authors: Song Ying-Qiu , Wang Nan , Qiao Yun , He Lei , Li Xia , Zhang Xiao-Fang , Yang Qian-Kun , Wang Run-Ze , He Rong , Wang Chen-Yu , Ren Yang-Wu , Li Guang , Wang Tian-Lu 
Published: January 2020

Abstract
Purpose
In this retrospective study, we evaluated the treatment patterns and survival after positron emission tomography-computed tomography (PET/CT)-guided local consolidation therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC).

Methods
We reviewed the medical records of Chinese patients with oligometastatic stage IV non-small cell lung cancer (≤ 5 metastases) who had undergone PET/CT and were eligible for systemic therapy at two centers between May 2005 and August 2019. Propensity score matching (1:1) was used to reduce selection bias and imbalanced distribution of confounding factors.

Results
We identified 84 eligible patients and used propensity scores to create well-matched groups of 35 patients who did or did not undergo LCT. Among all patients, the 1-year overall survival (OS) rate was 47.6% and the 2-year OS rate was 22.6%. Relative to the group that did not receive LCT, the LCT group had a significantly higher OS rate (13 months vs. 7 months, p = 0.002). The two groups had similar incidences and classifications of LCT-related side effects. In multivariable analysis, LCT was found to be strongly associated with a favorable OS (hazard ratio: 0.508, 95% confidence interval: 0.311–0.828, p = 0.001).

Conclusion
We concluded that LCT was significantly associated with improved clinical outcomes among the Chinese patients with oligometastatic NSCLC who were eligible for systemic treatment and could undergo PET/CT evaluation.
Mathematical modelling supports the existence of a threshold hydrogen concentration and media-dependent yields in the growth of a reductive acetogen
Authors: Smith Nick W. , Shorten Paul R. , Altermann Eric , Roy Nicole C. , McNabb Warren C. 
Published: January 2020

AbstractThe bacterial production of acetate via reductive acetogenesis along the Wood–Ljungdahl metabolic pathway is an important source of this molecule in several environments, ranging from industrial bioreactors to the human gastrointestinal tract. Here, we contributed to the study of reductive acetogens by considering mathematical modelling techniques for the prediction of bacterial growth and acetate production. We found that the incorporation of a hydrogen uptake concentration threshold into the models improves their predictions and we calculated this threshold as 86.2 mM (95% confidence interval 6.1–132.6 mM). Monod kinetics and first-order kinetics models, with the inclusion of two candidate threshold terms or reversible Michaelis–Menten kinetics, were compared to experimental data and the optimal formulation for predicting both growth and metabolism was found. The models were then used to compare the efficacy of two growth media for acetogens. We found that the recently described general acetogen medium was superior to the DSMZ medium in terms of unbiased estimation of acetogen growth and investigated the contribution of yeast extract concentration to acetate production and bacterial growth in culture. The models and their predictions will be useful to those studying both industrially and environmentally relevant reductive acetogenesis and allow for straightforward adaptation to similar cases with different organisms.
Tracking changes in user activity from unlabelled smart home sensor data using unsupervised learning methods
Authors: Gupta Prankit , McClatchey Richard , Caleb-Solly Praminda 
Published: January 2020

AbstractThis paper investigates the utility of unsupervised machine learning and data visualisation for tracking changes in user activity over time. This is done through analysing unlabelled data generated from passive and ambient smart home sensors, such as motion sensors, which are considered less intrusive than video cameras or wearables. The challenge in using unlabelled passive and ambient sensors data for activity recognition is to find practical methods that can provide meaningful information to support timely interventions based on changing user needs, without the overhead of having to label the data over long periods of time. The paper addresses this challenge to discover patterns in unlabelled sensor data using kernel density estimation (KDE) for pre-processing the data, together with t-distributed stochastic neighbour embedding and uniform manifold approximation and projection for visualising changes. The methodology is developed and tested on the Aruba CASAS smart home dataset and focusses on discovering and tracking changes in kitchen-based activities. The traditional approach of using sliding windows to segment the data requires a priori knowledge of the temporal characteristics of activities being identified. In this paper, we show how an adaptive approach for segmentation, KDE, is a suitable alternative for identifying temporal clusters of sensor events from unlabelled data that can represent an activity. The ability to visualise different recurring patterns of activity and changes to these over time is illustrated by mapping the data for separate days of the week. The paper then demonstrates how this can be used to track patterns over longer time-frames which could be used to help highlight differences in the user’s day-to-day behaviour. By presenting the data in a format that can be visually reviewed for temporal changes in activity over varying periods of time from unlabelled sensor data, opens up the opportunity for carers to then initiate further enquiry if variations to previous patterns are noted. This is seen as an accessible first step to enable carers to initiate informed discussions with the service user to understand what may be causing these changes and suggest appropriate interventions if the change is found to be detrimental to their well-being.
Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients
Authors: Huygens Simone A. , Ramos Isaac Corro , Bouten Carlijn V. C. , Kluin Jolanda , Chiu Shih Ting , Grunkemeier Gary L. , Takkenberg Johanna J. M. , Rutten-van Mölken Maureen P. M. H. 
Published: January 2020

AbstractObjectivesAortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions.MethodsUsing a patient-level simulation model, the potential cost-effectiveness of TEHV compared with bioprostheses was predicted from a societal perspective. Anticipated, but currently hypothetical improvements in performance of TEHV, divided in durability, thrombogenicity, and infection resistance, were explored in scenario analyses to estimate quality-adjusted life-year (QALY) gain, cost reduction, headroom, and budget impact.ResultsDurability of TEHV had the highest impact on QALY gain and costs, followed by infection resistance. Improved TEHV performance (− 50% prosthetic valve-related events) resulted in lifetime QALY gains of 0.131 and 0.043, lifetime cost reductions of €639 and €368, translating to headrooms of €3255 and €2498 per hypothetical TEHV compared to SAVR and TAVI, respectively. National savings in the first decade after implementation varied between €2.8 and €11.2 million (SAVR) and €3.2–€12.8 million (TAVI) for TEHV substitution rates of 25–100%.ConclusionsDespite the relatively short life expectancy of elderly patients undergoing SAVR/TAVI, hypothetical TEHV are predicted to be cost-effective compared to bioprostheses, commercially viable and result in national cost savings when biomedical engineers succeed in realising improved durability and/or infection resistance of TEHV.
High-energy events in the Frasnian–Famennian boundary interval of the Płucki section in the Holy Cross Mountains, Poland
Authors: Szrek Piotr , Salwa Sylwester 
Published: January 2020

AbstractOf all the Devonian stratigraphic boundaries, the Frasnian–Famennian transition (372.2 ± 1.6 Ma) preserves the record of one of the most significant crises in the history of life, the final stages of which lie buried in the distinctive Kellwasser limestone. The Kellwasser facies occur in Western and Central Europe and the commonly cited Płucki area of Poland’s geologically rich Holy Cross Mountains is the only site in that region where the Frasnian–Famennian boundary is considered to occur within Kellwasser facies. At this locality, the limestone contains slump structures, comprising contorted beds and folds. Actually the Kellwasser-like limestone from Płucki is composed of a mixture of three distinct types of sediment, occurring as clasts, commonly deformed and sheared, and matrix, rather than being one homogenous bed, as previously considered. Thus, earlier studies and interpretations of this limestone may need revising. This paper documents the evidence for sediment erosion and reworking, debris flows, sliding and soft-sediment deformation on a submarine slope, and suggests that seismic events were the likely triggering mechanism for slumping and resedimentation.
Assignment constraints in shared transportation services
Authors: Gansterer Margaretha , Hartl Richard F. , Wieser Sarah 
Published: January 2020

AbstractCompetitive markets, increased fuel costs, and underutilized vehicle fleets are characteristics that currently define the logistics sector. Given an increasing pressure to act in a manner that is economically and ecologically efficient, mechanisms that help to benefit from idle capacities are on the rise. In the Sharing Economy, collaborative usage is typically organized through platforms that facilitate the exchange of goods or services. Our study examines a collaborative pickup and delivery problem where carriers can exchange customer requests. The aim is to quantify the potential of horizontal collaborations under a centralized framework. An Adaptive Large Neighborhood Search is developed to solve yet unsolved test instances. A computational study confirms the results of past studies which have reported cost savings between 20 and 30%. In addition, the numerical results indicate an even greater potential for settings with a high degree of regional customer overlap. Unfortunately, these high collaborative gains typically come at the cost of an uneven customer distribution, which is known to be one of the main barriers that prevent companies from entering into horizontal collaborations. To generate acceptable solutions for all participants, several constraints are included in the model. The introduction of these constraints to single-vehicle instances, decreases the potential collaborative gain considerably. Surprisingly, this does not happen in more realistic settings of carriers operating multiple vehicles. Overall, the computational study shows that centralized collaborative frameworks have the potential to generate considerable cost savings, while at the same time limiting customer or profit share losses and enabling carriers to keep some of their most valued customers.
Range-wide patterns of human-mediated hybridisation in European wildcats
Authors: Tiesmeyer Annika , Ramos Luana , Manuel Lucas José , Steyer Katharina , Alves Paulo C. , Astaras Christos , Brix Mareike , Cragnolini Margherita , Domokos Csaba , Hegyeli Zsolt , Janssen René , Kitchener Andrew C. , Lambinet Clotilde , Mestdagh Xavier , Migli Despina , Monterroso Pedro , Mulder Jaap L. , Schockert Vinciane , Youlatos Dionisios , Pfenninger Markus , Nowak Carsten 
Published: January 2020

AbstractHybridisation between wild taxa and their domestic congeners is a significant conservation issue. Domestic species frequently outnumber their wild relatives in population size and distribution and may therefore genetically swamp the native species. The European wildcat (Felis silvestris) has been shown to hybridise with domestic cats (Felis catus). Previously suggested spatially divergent introgression levels have not been confirmed on a European scale due to significant differences in the applied methods to assess hybridisation of the European wildcat. We analysed 926Felisspp. samples from 13 European countries, using a set of 86 selected ancestry-informative SNPs, 14 microsatellites, and ten mitochondrial and Y-chromosome markers to study regional hybridisation and introgression patterns and population differentiation. We detected 51 hybrids (four F1 and 47 F2 or backcrosses) and 521 pure wildcats throughout Europe. The abundance of hybrids varied considerably among studied populations. All samples from Scotland were identified as F2 hybrids or backcrosses, supporting previous findings that the genetic integrity of that wildcat population has been seriously compromised. In other European populations, low to moderate levels of hybridisation were found, with the lowest levels being in Central and Southeast Europe. The occurrence of distinct maternal and paternal markers between wildcat and domestic cat suggests that there were no severe hybridisation episodes in the past. The overall low (< 1%) prevalence of F1 hybrids suggests a low risk of hybridisation for the long-term genetic integrity of the wildcat in most of Europe. However, regionally elevated introgression rates confirm that hybridisation poses a potential threat. We propose regional in-depth monitoring of hybridisation rates to identify factors driving hybridisation so as to develop effective strategies for conservation.
Pupil Response to Affective Stimuli: a Biomarker of Early Conduct Problems in Young Children
Authors: Burley Daniel T. , van Goozen Stephanie H.M. 
Published: January 2020

AbstractChildhood conduct problems have been associated with reduced autonomic arousal to negative cues indicative of an insensitivity to aversive stimuli, with mixed evidence in response to positive cues. Autonomic arousal to affective stimuli has traditionally been measured through galvanic skin responses and heart-rate, despite evidence that pupillometry is more reliable and practically beneficial (i.e., no wires are attached to the participant). The current study is the first to examine abnormal pupillary responsivity to affective stimuli as a biomarker for childhood conduct problems. We measured pupil reactivity to negative, positive and neutral images in 131 children aged 4–7 years, who were referred by their teachers for being at risk of future psychopathology. We assessed relationships between pupil response to the images and teacher-rated scores on the Strengths and Difficulties Questionnaire (SDQ), which indexed child conduct problems and their overlapping emotional, behavioural and social difficulties. Reduced pupil dilation to negative images was associated with significantly increased conduct, hyperactivity, emotional and peer problems, as well as reduced prosocial behaviour. Composite scores for disruptive behaviour and emotional difficulties both uniquely predicted blunted pupil response to negative threat stimuli; there were no relations with pupil responses to positive images. These findings highlight that blunted pupil responsivity to negative stimuli serves as a biomarker for early disruptive behavioural problems and affective difficulties. Pupillometry offers an inexpensive, fast and non-intrusive measure to help identify children who are showing early disruptive behaviour or experiencing affective difficulties, which can provide opportunities for preventative intervention to avoid further psychopathology.
Semiparametric regression and risk prediction with competing risks data under missing cause of failure
Authors: Bakoyannis Giorgos , Zhang Ying , Yiannoutsos Constantin T. 
Published: January 2020

AbstractThe cause of failure in cohort studies that involve competing risks is frequently incompletely observed. To address this, several methods have been proposed for the semiparametric proportional cause-specific hazards model under a missing at random assumption. However, these proposals provide inference for the regression coefficients only, and do not consider the infinite dimensional parameters, such as the covariate-specific cumulative incidence function. Nevertheless, the latter quantity is essential for risk prediction in modern medicine. In this paper we propose a unified framework for inference about both the regression coefficients of the proportional cause-specific hazards model and the covariate-specific cumulative incidence functions under missing at random cause of failure. Our approach is based on a novel computationally efficient maximum pseudo-partial-likelihood estimation method for the semiparametric proportional cause-specific hazards model. Using modern empirical process theory we derive the asymptotic properties of the proposed estimators for the regression coefficients and the covariate-specific cumulative incidence functions, and provide methodology for constructing simultaneous confidence bands for the latter. Simulation studies show that our estimators perform well even in the presence of a large fraction of missing cause of failures, and that the regression coefficient estimator can be substantially more efficient compared to the previously proposed augmented inverse probability weighting estimator. The method is applied using data from an HIV cohort study and a bladder cancer clinical trial.