bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive morality and the realization of freedom in Kant's moral philosophy
Authors: Biss Mavis 
Published: December 2018

AbstractThis paper argues that recent accounts of Kantian virtue as “strengthened” inner freedom apply much more clearly to the avoidance of violations of perfect duties than to the fulfillment of imperfect duties, leaving us with the question of how inadequate commitment to morally required ends impacts the exercise of inner freedom. The question is answered through the development of a model of inner freedom that emphasizes the relationship between moral self‐governance and participation in an ethical community.
Study of the NR4A family gene expression in patients with multiple sclerosis treated with Fingolimod
Authors: Montarolo F. , Perga S. , Martire S. , Brescia F. , Caldano M. , Lo Re M. , Panzica G. , Bertolotto A. 
Published: December 2018

Background and purposeFingolimod is a drug approved for treatment of relapsing‐remitting multiple sclerosis (RRMS) that exerts its effects via sequestering lymphocytes within the lymph nodes. The drug, acting on the sphingosine‐1‐phosphate pathway, is involved in a plethora of processes and, to date, its mechanism of action is not completely understood.Recently, it has been demonstrated that Fingolimod increases the expression of transcription factor NR4A2 in murine brain. NR4A2 belongs to nuclear receptor family 4, group A (NR4A) along with NR4A1 and NR4A3. The role of NR4A2 in the pathogenesis of multiple sclerosis is already known and supported by its down‐regulation observed in blood obtained from patients with RRMS compared with healthy controls (HCs). It is notable that NR4A2 impairment is reversed in patients with RRMS during pregnancy, which represents a transitory state of immune tolerance, associated with reduced disease activity. An inverse correlation between NR4A2 gene expression levels and clinical parameters indicates that more aggressive forms of the disease are characterized by lower levels of NR4A2.MethodsGene expression levels of NR4A in blood obtained from HCs, treatment‐naive (T0) and Fingolimod‐treated patients with RRMS were evaluated to determine their contribution to drug response.ResultsGene expression levels of NR4A were down‐regulated in T0 patients compared with HCs. Patients treated with Fingolimod for >2 years were characterized by higher levels of NR4A2 compared with the T0 group, approaching those of HCs. NR4A1 and NR4A3 levels were not altered.ConclusionsInvolvement of the NR4A family in the pathogenesis of multiple sclerosis and a role of Fingolimod in the recovery from NR4A2 deficit can be hypothesized based on our data.
Intravenous thrombolysis in wake‐up stroke: real‐world data from the Austrian Stroke Unit Registry
Authors: Krebs S. , Posekany A. , Ferrari J. , Lang W. , Sommer P. , Gattringer T. , Boehme C. , Sykora M. ,   the Austrian Stroke Unit Registry Collaborators
Published: December 2018

Background and purposeData on real‐world experience with intravenous thrombolysis (IV tPA) in wake‐up stroke (WUS) are limited. The aim of this study was to examine the efficacy and safety of IV tPA in patients with WUS included in the Austrian Stroke Unit Registry.MethodsData from a large nationwide stroke unit registry including initial stroke severity, vascular risk factors, comorbidities, treatment with IV tPA, symptomatic intracerebral haemorrhage (sICH) and functional outcome were extracted and analysed. Patients with WUS were compared with patients with known‐onset stroke (KOS) regarding the frequency of IV tPA treatment, neurological improvement (National Institutes of Health Stroke Scale score ≥4), sICH and 3‐month functional outcome by modified Rankin Scale score using standard statistical tests.ResultsA total of 107 895 stroke patients entered the analysis, including 12 534 with WUS and 91 899 with KOS. Altogether, 904 (7.2%) patients with WUS received IV tPA as compared with 16 694 (18.2%) patients with KOS. Patients with WUS who received IV tPA treatment had twofold higher initial National Institutes of Health Stroke Scale score (median 8 vs. median 4) as compared with patients with KOS. There was no statistical difference in functional outcome by modified Rankin Scale score 0–1 at 3 months between patients with WUS and patients with KOS treated with IV tPA (adjusted odds ratio, 1.08; 95% confidence interval, 0.9–1.31). Also, the rate of sICH did not differ (4.1% vs. 4%, P = 0.852).ConclusionsIn this large non‐randomized comparison, the safety and efficacy of IV tPA in patients with WUS in the real‐world setting seems to be comparable to patients with KOS.
The ADAN scale: a proposed scale for pre‐hospital use to identify status epilepticus
Authors: Requena M. , Fonseca E. , Olivé M. , Abraira L. , Quintana M. , Mazuela G. , Toledo M. , Salas‐Puig X. , Santamarina E. 
Published: December 2018

Background and purposeThe prognosis of status epilepticus (SE) depends on the time between onset and the diagnosis and start of treatment. Our aim was to design a scale with predictive value for pre‐hospital diagnosis of SE.MethodsThis was a retrospective study of 292 patients who attended the emergency department for an epileptic seizure. A total of 49 patients fulfilled the criteria for SE. We recorded the patients’ history and clinical features. Variables independently associated with SE were combined to design a clinical scale. The performance of the scale was evaluated in a validation dataset of 197 patients.ResultsA total of 50.3% of the patients were male and the mean age was 55.9 years. The following features were more prevalent in patients with SE: abnormal speech (79.6% vs. 18.9%, P < 0.001), eye deviation (69.4% vs. 14.0%, P < 0.001), automatism (22.4% vs. 6.3%, P < 0.001), hemiparesis (24.5% vs. 10.9%, P = 0.011), state of stupor/coma (46.9% vs. 4.2%, P < 0.001) and number of pre‐hospital seizures, i.e. two (34.7% vs. 4.5%, P < 0.001) or more than two (51.0% vs. 0.4%, P < 0.001). Based on these findings, we designed a scale that scored 1 point each for presence of abnormal speech, eye deviation, automatism and two seizures, and 2 points for more than two seizures. The predictive capacity of the scale for identifying SE in the validation dataset was 98.7% (95% confidence interval, 97.3%–100%) and 85.4% of patients with a score >1 had SE.ConclusionsA score >1 on the ADAN scale is a robust predictor of the diagnosis of SE in patients who experience an epileptic seizure. This scale may be a useful tool for clinical use and warrants further investigation.
Postictal electroencephalographic (EEG) suppression: A stereo‐EEG study of 100 focal to bilateral tonic–clonic seizures
Authors: Marchi Angela , Giusiano Bernard , King Mark , Lagarde Stanislas , Trébuchon‐Dafonseca Agnès , Bernard Christophe , Rheims Sylvain , Bartolomei Fabrice , McGonigal Aileen 
Published: December 2018

SummaryObjectivesWe aimed to describe intracerebral aspects of postictal generalized electroencephalography suppression (PGES) following focal to bilateral tonic–clonic (“secondarily generalized tonic–clonic”) seizures (GTCS) recorded using stereoelectroencephalographic (SEEG), and to correlate these with electroclinical features.MethodsThree independent observers scored semiologic and SEEG features. Patient and epilepsy characteristics were collected. Descriptive statistics and multivariate analysis were performed. The operational definition of PGES on SEEG used strict criteria (absence of visible signal at 20 μV/mm amplitude, in all readable channels). Postictal regional suppression (RS) was identified if only a subset of implanted electrodes showed absence of signal.ResultsWe evaluated 100 seizures in 52 patients. Interobserver agreement was good (κ 0.72 for clinical features and 0.73 for EEG features). PGES was present in 27 of 100 and RS without PGES present in 42 of 100 seizures. Region of RS included epileptogenic zone in 43 of 51 (86%). No effect of sampling (multilobar or bilateral exploration) was seen. Oral tonicity (mouth opening and/or tonic vocalization during the tonic phase of GTCS) was associated with the presence of PGES (P = 0.029; negative predictive value [NPV] 0.91). Bilateral upper limb extension during the tonic phase correlated with PGES (P = 0.041; NPV 0.85). Association of both oral tonicity and bilateral upper limb extension had a high NPV of 0.96.SignificanceSEEG recordings confirm true absence of signal during postictal EEG suppression. PGES is unlikely when both upper limb extension and oral tonicity are absent. We hypothesize that bilateral tonic seizure discharge at bulbar level brainstem regions is associated with the production of oral signs and may relate to mechanisms of PGES.
Tissue microenvironment initiates an immune response to structural components of Staphylococcus aureus
Authors: Mainzer Carine , Packard Thomas , Bordes Sylvie , Closs Brigitte , Greene Warner C. , Elias Peter M. , Uchida Yoshikazu 
Published: December 2018

AbstractCell‐to‐cell communication in skin participates to the maintenance of homeostatic responses to foreign substances. Certain strains of Staphylococcus (S) aureus are vicious pathogens that cause deleterious effects in host cells and tissues. Both secreted toxins and structural components of S. aureus trigger an immune response, though how S. aureus stimulates host immune responses is poorly understood. We explored here how keratinocytes and fibroblasts initiate the first steps of an immune response by activating dendritic cells (DCs) through recognition of structural components of S. aureus. We treated monocyte‐derived Langerhans cells (moLCs) and monocyte‐derived DCs (moDCs) with conditioned media from keratinocytes (K‐CM) and fibroblasts (F‐CM) treated with heat‐killed S. aureus (HKSA) respectively, or directly with HKSA. Immune and inflammatory responses from keratinocytes, fibroblasts, moLCs and moDCs were assessed by analysis of cell surface markers and cytokine production using flow cytometry, real‐time PCR and ELISA assays. K‐CM and F‐CM increased the expression of CD86 and HLA‐DR on moLCs and moDCs, in association with a specific cytokine profile. K‐CM upregulated TNFA, IL‐1B and GM‐CSF mRNA expression in moLCs, while F‐CM upregulated IL‐12 and downregulated TNFA and TGFB mRNA expression in moDCs. Additionally, F‐CM attenuated the induction of an inflammatory profile in monocytes. The recognition of structural components from S. aureus by cutaneous microenvironment induces the activation and the expression of specific cytokines from LCs and DCs.
Oral health‐related quality of life in older adults—Longitudinal study
Authors: Echeverria Mariana S. , Wünsch Isadora S. , Langlois Caroline O. , Cascaes Andreia M. , Ribeiro Silva Alexandre E. 
Published: December 2018

ObjectiveThe aim of the present study was to investigate oral health‐related quality of life (OHRQoL) and determine associations with demographic, socio‐economic and oral health variables at two evaluation times (2009 and 2015) among older adults assisted by Family Health Units in the Brazil.MethodsA longitudinal study was conducted involving the evaluation (2009) and re‐evaluation (2015) of 161 older adults (≥60 years of age). Demographic, socio‐economic and general health variables were collected using a standardised questionnaire. Clinical oral health variables were also collected. OHRQoL was measured using the Oral Health Impact Profile‐14 (OHIP‐14). Multiple regression analysis was employed for the evaluation of OHRQoL considering the variables from the two evaluations.ResultsThe severity of impact (mean OHIP‐14) was 9.12 (SD: 10.81) in 2009 and 8.50 (10.52) in 2015. The greatest impact regarded the psychological discomfort domain at both evaluations (28.8% in 2009 and 22.9% in 2015). In the adjusted multiple linear regression, the mean OHIP‐14 score increased 4.8 points (95% CI: 0.11‐9.49) among individuals who experienced tooth loss between the two evaluations in comparison with those who maintained the same number of teeth. An increase in the OHIP‐14 score occurred between 2009 and 2015 among 40.6% of the older adults.ConclusionsThe findings of the present study reveal that the oral health status of older adults exerts an influence on OHRQoL, indicating the need for oral health policies directed at this portion of the population.
Predictors of mortality in older patients admitted to a geriatric hospital
Authors: Agrawal Siddarth , Luc Mateusz , Winkowski Filip , Lindner Karolina , Agrawal Anil Kumar , Wozniak Marta , Sobieszczanska Malgorzata 
Published: December 2018

AimThe identification of older patients at risk of mortality is important to provide properly tailored care and effectively manage healthcare resources. The present study aimed to identify predictors of all‐cause mortality related to geriatric patients’ clinical, functional and sociodemographic status at admission.MethodsA retrospective study was carried out of patients admitted to a geriatric hospital from January to May 2013. A total of 208 patients were enrolled in the study. The outcome measure was 4‐year mortality.ResultsThe mortality rate was 26%. We found that age, red blood cells count and white blood cells count, as well as C‐reactive protein level, albumin level and high‐density lipoprotein cholesterol level significantly correlated with mortality. Furthermore, the presence of clinical symptoms, such as pressure ulcers and depressed level of consciousness, was predictive of poor outcome. Multidimensional aspects of aging that are assessed in the Comprehensive Geriatric Assessment – activities of daily living, instrumental activities of daily living, Barthel scale, Mini‐Mental State Examination and The Clock Drawing Test – appeared to be strong predictors of 4‐year mortality. The expression to estimate the probability of mortality based on the examined variables correctly classified nearly 85% of the analyzed cases.ConclusionsEarly detection of high‐risk patients is of particular significance to reach a better survival rate among older adults. Clinicians should put more stress on the comprehensive surveillance of geriatric patients, rather than focusing solely on the treatment of chronic diseases.Geriatr Gerontol Int 2019; 19: 70–75.
Analysis of 307 cases with drug‐induced liver injury between 2010 and 2018 in Japan
Authors: Aiso Mitsuhiko , Takikawa Hajime , Tsuji Keiji , Kagawa Tatehiro , Watanabe Masaaki , Tanaka Atsushi , Sato Ken , Sakisaka Shotaro , Hiasa Yoichi , Takei Yoshiyuki , Ohira Hiromasa , Ayada Minoru , Hashimoto Etsuko , Kaneko Shuichi , Ueno Yoshiyuki , Ohmoto Kenji , Takaki Akinobu , Torimura Takuji , Matsuzaki Yasushi , Tajiri Kazuto , Yoneda Masashi , Ito Takayoshi , Kato Naoya , Ikejima Kenichi , Mochida Satoshi , Yasuda Hiroshi , Sakamoto Naoya 
Published: December 2018

AimIn order to know the present status of drug‐induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals.MethodsDrug‐induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria.ResultsIn total, data of 307 cases (125 male and 182 female individuals) aged between 17 and 86 years old were collected. The types of liver injury were as follows: 64% hepatocellular type, 20% mixed type, and 16% cholestatic type. A drug‐induced lymphocyte stimulation test was carried out in 59% of cases, and was positive in 48% and semipositive in 3% of cases. Eosinophilia ≥6% was observed in 27% of cases. Fifty‐three percent of DILI cases occurred within 30 days and 79% of DILI cases occurred within 90 days after starting drug administration. By the diagnostic scale of the Digestive Disease Week (DDW)‐Japan 2004 workshop, 93.8% of cases were diagnosed as “highly probable”, and 5.9% as “possible”.ConclusionsJapanese DILI patients are somewhat different from those of Europe and North America. The diagnostic scale of the DDW‐Japan 2004 workshop has been used in Japan. However, there are many issues to improve the causality assessment of DILI that we must investigate in the future. It is critical to elucidate the mechanisms of drug metabolism and the pathophysiology of liver injury by various drugs to prevent DILI.
“I kind of gave up on it after a while, became too hard, closed my eyes, didn't want to know about it”—adults with type 1 diabetes mellitus describe defeat in the context of low social support
Authors: Hill Kathleen , Ward Paul , Gleadle Jonathan 
Published: December 2018

AbstractBackgroundType 1 diabetes mellitus (T1DM) is a lifelong condition that requires diligent self‐management to avoid complications. Living with T1DM is a considerable challenge and the inability to follow a prescribed regimen is often termed non‐compliance. However, this fails to acknowledge that for some people the barriers to glycaemic control may be insurmountable.ObjectiveThis qualitative study explores the structural determinants, social context and lived experience of T1DM with 17 adults to understand influences on patterns of self‐care, engagement with and trust in health‐care services, and health outcomes.ResultsTheir stories tell us that strong social support is vital to disease adaptation and ongoing management. When social support is absent, the story is one of struggling with intensive diabetes management alone and difficulty controlling blood glucose levels. When confronted with suboptimal glycaemic control, participants isolated from social support developed combative relationships with health‐care providers and disengaged from health care. Their subsequent slide to chronic comorbid illness is steep and this study reveals the heartache and loss experienced when difficult life circumstances and low levels of social support have led to irreparable kidney damage.ConclusionPatterns of poor glycaemic control viewed in the health‐care encounter without an understanding of the context or life circumstances in which they are occurring can lead to an inability to engage with health‐care services. Disengagement from services and the absence of specialist care further isolates people, leaving them managing their diabetes alone with limited success.
Somatic genetic alterations in synchronous and metachronous low‐grade serous tumours and high‐grade carcinomas of the adnexa
Authors: Murali Rajmohan , Selenica Pier , Brown David N , Cheetham R Keira , Chandramohan Raghu , Claros Nidia L , Bouvier Nancy , Cheng Donavan T , Soslow Robert A , Weigelt Britta , McCluggage W Glenn 
Published: December 2018

AimsLow‐grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high‐grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high‐grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low‐grade serous tumours and synchronous or metachronous high‐grade adnexal carcinomas.Methods and resultsDNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non‐coding regions of 341 cancer‐related genes. The low‐grade and high‐grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low‐grade to high‐grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high‐grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively.ConclusionsOur results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low‐grade serous precursor.
A biological study of supernumerary teeth derived dental pulp stem cells based on RNA‐seq analysis
Authors: Lu X. , Liu S‐F. , Wang H‐H. , Yu F. , Liu J‐J. , Zhao Y‐M. , Zhao S‐L. 
Published: December 2018

AbstractAimTo identify the basic characteristics and gene expression profiles of supernumerary teeth derived stem cells (SNTSCs) and compare them with those of normal dental pulp stem cells (DPSCs).MethodologyFlow cytometry was conducted to identify the protein expression of stem cell markers. Cell proliferation, migration and differentiation abilities of both SNTSCs and DPSCs were determined by CCK8, transwell and differentiation assays, respectively. Gene expression profiles were studied by RNA sequencing analyses. After knocking down the expression of certain differential expression genes (DEGs), the function of DEGs was investigated by CCK8 and transwell assays. Statistical differences were determined using a two‐tailed t‐test and P values below 0.05 were considered significant.ResultsSupernumerary teeth derived stem cells were capable of differentiating into adipocyte, chondrocyte and osteoblast lineage cells, and compared to ordinary DPSCs, SNTSCs had a significantly higher cell proliferation rate (P < 0.01) and significantly lower migration rate (P < 0.01). RNA‐seq results revealed the differential expression genes (DEGs) between SNTSCs and DPSCs. A principal component analysis (PCA) and cluster analysis revealed that the gene expression patterns of SNTSCs and DPSCs were different from each other. A total of 12 861 genes were differentially expressed at a significant P value (P ≤ 0.01), and 5292 of these increased in SNTSCs and 7569 decreased. Further study on the selected DEGs revealed that FUT11, FAM155A and BRD2 inhibited the cell proliferation rate of SNTSCs, and FUT11 and GLUD1 inhibited the cell migration rate, whilst FAM155A promoted the migration rate.ConclusionsThe biological characteristics and gene expression profile of SNTSCs was revealed. The stem cell properties of SNTSCs were similar to normal DPSCs but they had a high cell proliferation rate and may have greater potential for cell differentiation.
Current understanding of transport and bioavailability of bioactive peptides derived from dairy proteins: a review
Authors: Xu Qingbiao , Yan Xianghua , Zhang Yangdong , Wu Jianping 
Published: December 2018

SummaryDairy protein‐derived bioactive peptides (DBPs) have potential benefits for human health. However, their transport mechanisms and bioavailability from intestinal lumen to bloodstream are not well understood. This review summarises current understanding of their transport mechanisms across the intestinal membrane (peptide transport 1, paracellular route, transcytosis and passive transcellular diffusion) and the bioavailability of DBPs in animal and human studies. Some DBPs can escape the degradation of peptidase and reach the bloodstream at concentrations of micromolar range, and keep intact for several minutes to hours. The presences of brush‐border peptidases at the site of absorption and other peptidases in the blood, along with the peptide properties, such as molecular size and weight, stability to proteases, hydrophobicity and charge, determine their bioavailability. Developing novel analytical tools for accurate measurement and study of the transport, metabolism, and bioavailability of DBPs in vivo are expected.