bluuebunny/crossref_metadata_2025_split huggingface dataset:
Language Games in the Ivory Tower: Comparing the Philosophical Investigations with Hermann Hesse’s The Glass Bead Game
Authors: Edwards Georgina 
Published: December 2019

Abstract
Wittgenstein explores learning through practice in the Philosophical Investigations by means of an extended analogy with games. However, does this concern with learning also necessarily extend to education, in our institutional understanding of the word? While Wittgenstein's examples of language learning and use are always shared or social, he does not discuss formal educational institutions as such. He does not wish to found a ‘school of thought’, and is suspicious of philosophy acting as a theory that can be applied to other areas of life. While Wittgenstein's focus on developing independent thinking was neither individualistic nor anti-institutional, it did, however, focus on developing the thinking of his students rather than theorising about how this could be applied on a large scale. An analysis of Hermann Hesse's novel, The Glass Bead Game will help us to pick up where Wittgenstein deliberately left off—thinking about how (or if) one can institutionalise learning methods that encourage thinking for oneself. These differences in the writers’ treatment of education will become evident in the differences between their game analogies. While language-games combat our ‘craving for generality’ in Philosophical Investigations, the Glass Bead Game represents this craving, and how it manifests itself throughout history in disciplines other than logic and philosophy of language. It also represents the potential for institutions to become insular, exclusive communities.
Three‐Dimensional Prediction of the Nose for Facial Approximation in a Thai Population
Authors: Thitiorul Sumon , Mahakkanukrauh Pasuk , Prasitwattanaseree Sukon , Sitthiseripratip Kriskrai , Iamaroon Anak , Na Lampang Sakarat , Prapayasatok Sangsom 
Published: December 2019

AbstractMost of the previous studies about nose prediction were concentrated only some landmarks of the nose. This study aimed to generate prediction equations for ten landmarks of the nose in the midline and alar regions for forensic facial approximation. The six midline landmarks were the sellion, nasion–pronasale posterior, nasion–pronasale anterior, pronasale, nasal drop, and subnasale. The four landmarks of the alar region were the alare, superior alar groove, posterior alar groove, and inferior alar groove. We used the skull landmarks in the nasal, zygomatic, and maxillary bone to predict the landmarks of the nose. Cone‐beam computed tomography scans of 108 Thai subjects with normal BMI and age ranging from 21.0 to 50.9 years were obtained in a sitting position. The data were converted into three‐dimensional (3‐D) images of the skull and face. The Cartesian coordinates of the landmarks of the skull and nose were used to formulate the multiple regression equations. The formulated equations were tested in 24 new subjects. The mean differences in the predicted midline landmarks varied between −0.4 mm and 0.5 mm, whereas those for bilateral landmarks varied between −1.0 mm and 1.4 mm. In conclusion, the prediction equations formulated here will be beneficial for facial approximation of the nose in a Thai population.
A Mini‐Review on Brewer's Spent Grain Protein: Isolation, Physicochemical Properties, Application of Protein, and Functional Properties of Hydrolysates
Authors: Wen Chaoting , Zhang Jixian , Duan Yuqing , Zhang Haihui , Ma Haile 
Published: December 2019

AbstractThere is a growing demand in reusing agro‐industrial waste to enrich food proteins and develop new protein‐related products. Brewer's spent grain (BSG), the byproducts generated from the processing of beer‐brewing industry, is rich in abundant protein (26 to 30%) with good physicochemical properties and nutritional benefits. BSG is mainly composed of four proteins including hordein, gluten, globulin, and albumin. The methods for extracting protein from BSG mainly include alkali extraction, ultrasonic‐assisted extraction, and organic solvent extraction, among others. However, little researches have described the functional properties of Brewer's spent grain protein (BSGP) and how it can be improved by enzymatic modification. Additionally, BSG protein hydrolysates (BSGPHs) have good bioactivities, mainly including antioxidant, antiinflammatory, and angiotensin‐I–converting enzyme inhibitory activities, among others. Based on the above situation, this review provides a comprehensive overview about the isolation, physicochemical features, application of the BSGP. In addition, the functional properties and biological activities of BSGPHs are also emphasized. The purpose of this review is to provide an up‐to‐date summary of BSGP research, and to broaden the market potential of this emerging protein in food industry. Besides, this review provides a reference to study the use of BSGP or hydrolysates for a variety of purposes in‐depth, including pharmaceutical, food, and industrial applications.
Measuring biological aging in humans: A quest
Authors: Ferrucci Luigi , Gonzalez‐Freire Marta , Fabbri Elisa , Simonsick Eleanor , Tanaka Toshiko , Moore Zenobia , Salimi Shabnam , Sierra Felipe , de Cabo Rafael 
Published: December 2019

AbstractThe global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.
Behavioral sensitization and cellular responses to psychostimulants are reduced in D2R knockout mice
Authors: Solís Oscar , García‐Sanz Patricia , Martín Ana B. , Granado Noelia , Sanz‐Magro Adrián , Podlesniy Petar , Trullas Ramón , Murer M. Gustavo , Maldonado Rafael , Moratalla Rosario 
Published: December 2019

AbstractRepeated cocaine exposure causes long‐lasting neuroadaptations that involve alterations in cellular signaling and gene expression mediated by dopamine in different brain regions, such as the striatum. Previous studies have pointed out to the dopamine D1 receptor as one major player in psychostimulants‐induced behavioral, cellular, and molecular changes. However, the role of other dopamine receptors has not been fully characterized. Here we used dopamine D2 receptor knockout (D2−/−) mice to explore the role of D2 receptor (D2R) in behavioral sensitization and its associated gene expression after acute and chronic cocaine and amphetamine administration. We also studied the impact of D2R elimination in D1R‐mediated responses. We found that cocaine‐ and amphetamine‐induced behavioral sensitization is deficient in D2−/−mice. The expression of dynorphin, primarily regulated by D1R and a marker of direct‐pathway striatal neurons, is attenuated in naïve‐ and in cocaine‐ or amphetamine‐treated D2−/−mice. Moreover, c‐Fos expression observed in D2−/−mice was reduced in acutely but not in chronically treated animals. Interestingly, inactivation of D2R increased c‐Fos expression in neurons of the striatopallidal pathway. Finally, elimination of D2R blunted the locomotor and striatal c‐Fos response to the full D1 agonist SKF81297. In conclusion, D2R is critical for the development of behavioral sensitization and the associated gene expression, after cocaine administration, and it is required for the locomotor responses promoted by D1R activation.
Titrated baclofen for high‐risk alcohol consumption: a randomized placebo‐controlled trial in out‐patients with 1‐year follow‐up
Authors: Rigal Laurent , Sidorkiewicz Stéphanie , Tréluyer Jean‐Marc , Perrodeau Elodie , Le Jeunne Claire , Porcher Raphaël , Jaury Philippe 
Published: December 2019

AbstractBackground and AimsBaclofen is a promising drug for treating patients with alcohol‐related disorders. Nevertheless, the first randomized clinical trials (mainly with target doses) reported inconsistent efficacy, possibly because of the effective dose widely varying between patients. The Bacloville study aimed to test the efficacy of titrated baclofen for achieving low‐risk alcohol consumption.DesignTwelve‐month multicenter pragmatic double‐blind randomized clinical trial from June 2012 to June 2014.SettingSixty‐two French primary care centers.ParticipantsOut‐patients with high‐risk alcohol consumption (> 40 g/day for women and > 60 g/day for men).Intervention and comparatorPatients were randomly assigned (1 : 1 ratio) to receive titrated baclofen up to 300 mg/day or placebo for 12 months. Switching to open‐label baclofen was allowed in cases of perceived inefficacy.MeasurementsThe primary outcome defined success as no or low‐risk alcohol consumption (≤ 20 g/day for women and ≤ 40 g/day for men) during the last month of the 1‐year follow up, with patients who switched to open‐label baclofen classified as failures.FindingsA total of 320 patients were randomized, 162 to baclofen and 158 to placebo (consumption 129 g/day in both arms). Discontinuation rates were 30 and 34% in the baclofen and placebo arms, respectively, and return rates of the last‐month diaries were 42 and 34%, respectively. Primary success rates were 57 and 36% in the baclofen and placebo arms, respectively [difference: 21 percentage points, 95% confidence interval (CI) = 8–34, P = 0.003]. When switchers were not classified as failures unless they failed, the success rates were 62 versus 55% (difference: 6 percentage points, 95% CI = –7 to 20). Over 12 months, daily consumption differed between both arms (11 g less in the baclofen arm), as did the number of abstinence days (3.3 days more in the baclofen arm). Adverse events were more frequent with baclofen than placebo and were mostly drowsiness, fatigue and insomnia. Serious adverse events occurred in 85 (seven deaths) and 36 (three deaths) patients with baclofen and placebo, respectively.ConclusionsBaclofen was more effective than placebo in reducing alcohol consumption to low‐risk levels. The number of adverse events and more serious adverse events was greater with baclofen than placebo.
Marijuana use trends among college students in states with and without legalization of recreational use: initial and longer‐term changes from 2008 to 2018
Authors: Bae Harold , Kerr David C. R. 
Published: December 2019

AbstractBackground and aimsYoung adult college students in the United States are likely to be affected by marijuana liberalization trends. However, changes in students’ marijuana use following recreational marijuana legalization (RML) have not been examined in more than one RML state at a time, or beyond 1–2 years post‐legalization.DesignCross‐sectional National College Health Assessment survey administered twice yearly from 2008 to 2018.SettingA total of 587 4‐year colleges and universities in 48 US states.ParticipantsUndergraduates aged 18–26 years attending college in US states that did (n = 234 669 in seven states) or did not (n = 599 605 in 41 states) enact RML between 2008 and 2018.MeasurementsSelf‐reported marijuana use (past 30 days) and individual and contextual covariates, institution‐provided institutional and community covariates and publicly available dates when states enacted RML.FindingsAdjusting for covariates, state differences and state‐specific linear time trends (accounting for pre‐RML trends), prevalence of 30‐day marijuana use increased more among students exposed to RML [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.19–1.28, P < 0.001] than among non‐RML state students throughout the same time‐period; the results were similar for frequent use (≥ 20 days) (OR = 1.18, 95% CI = 1.10–1.27, P < 0.001). Interaction models supported stronger RML effects among students who were female, residing off‐campus and aged 21 years and older; sexual orientation did not moderate RML effects. In the earliest states to enact RML (2012) there were increases in use prevalence in the second through the sixth year post‐RML compared to pre‐RML. In the second legalization group (2015) there were increases in the first and second year post‐RML, and greater increases in the third year. In the later states (2016–17), increases were observed in both years after RML.ConclusionsIn US states that enacted recreational marijuana legislation from 2012 to 2017 there was evidence for a general trend towards greater increases in marijuana use by college students and differential impact by gender, legal using age and campus residence.
Predictors for trifecta achievement of robot‐assisted partial nephrectomy in high‐complexity tumors (Preoperative Aspects and Dimensions Used for an Anatomical score ≥10)
Authors: Takahara Kiyoshi , Sumitomo Makoto , Fukaya Kosuke , Jyoudai Takahito , Nishino Masashi , Hikichi Masaru , Nukaya Takuhisa , Zennami Kenji , Ichino Manabu , Fukami Naohiko , Sasaki Hitomi , Kusaka Mamoru , Shiroki Ryoichi 
Published: December 2019

AbstractIntroductionRobot‐assisted partial nephrectomy (RAPN) is emerging as an effective treatment oncologically and functionally for clinically localized renal tumors. However, RAPN in high‐complexity tumors with a Preoperative Aspects and Dimensions Used for an Anatomical score ≥10 remains challenging. In this study, the feasibility of RAPN for high‐complexity tumors was assessed.MethodsThe study cohort consisted of 177 cases with clinically localized renal cell carcinoma who had undergone RAPN at our hospital from July 2010 to February 2018. They were assessed for perioperative parameters and trifecta achievement (ie, negative surgical margins, warm ischemia time <25 minutes, and no complications).ResultsAmong the 177 cases who had undergone RAPN, 60 had high‐complexity tumors, and 117 had non‐high‐complexity (ie, intermediate‐ or low‐complexity) tumors. There were no significant differences in the operative and console times between the cohorts, but estimated intraoperative blood loss was much lower in the non‐high‐complexity group. Although the average warm ischemia time was less than 25 minutes in both groups, it was significantly shorter in the non‐high‐complexity group. Trifecta achievement rates significantly differed between the high‐ and non‐high‐complexity groups (68.3% vs 86.3%). Comparisons of four operative parameters (ie, BMI, tumor size, endophytic properties, and hilar tumor) using univariate analysis in the 60 high‐complexity tumor cases showed that BMI and tumor size were independent factors (P = 0.05 and 0.018, respectively). In multivariate analysis, tumor size was the only factor directly associated with trifecta achievement (P = 0.029).ConclusionThe trifecta achievement rate was significantly lower in the high‐complexity group. Only tumor size affected trifecta achievement during RAPN in cases with high‐complexity tumors (Preoperative Aspects and Dimensions Used for an Anatomical score ≥10).
Robustness of ANCOVA in randomized trials with unequal randomization
Authors: Bartlett Jonathan W. 
Published: December 2019

AbstractRandomized trials with continuous outcomes are often analyzed using analysis of covariance (ANCOVA), with adjustment for prognostic baseline covariates. The ANCOVA estimator of the treatment effect is consistent under arbitrary model misspecification. In an article recently published in the journal, Wang et al proved the model‐based variance estimator for the treatment effect is also consistent under outcome model misspecification, assuming the probability of randomization to each treatment is 1/2. In this reader reaction, we derive explicit expressions which show that when randomization is unequal, the model‐based variance estimator can be biased upwards or downwards. In contrast, robust sandwich variance estimators can provide asymptotically valid inferences under arbitrary misspecification, even when randomization probabilities are not equal.
Identify old drugs as selective bacterial β‐GUS inhibitors by structural‐based virtual screening and bio‐evaluations
Authors: Chen Zhou , Xu Xiaoshuang , Piao Lianhua , Chang Shan , Liu Jiyong , Kong Ren 
Published: December 2019

AbstractIrinotecan (CPT‐11) is a cytotoxic drug that has wide applicability and usage in cancer treatment. Despite its success, patients suffer dose‐dependent diarrhea, limiting the drug's efficacy. No effective therapy is available for this unmet medical need. The bacterial β‐glucuronidase (β‐GUS) plays pivotal role in CPT‐11‐induced diarrhea (CID) via activating the non‐toxic SN‐38G to toxic SN‐38 inside intestine. By using structural‐based virtual screening, three old drugs (N‐Desmethylclozapine, Aspartame, and Gemifloxacin) were firstly identified as selective bacterial β‐GUS inhibitors. The IC50 values of the compounds in the enzyme‐based and cell‐based assays range from 0.0389 to 3.6040 and 0.0105 to 5.3730 μM, respectively. The compounds also showed good selectivity against mammalian β‐GUS and no significant cytotoxicity in bacteria. Molecular docking and molecular dynamics simulations were performed to further investigate the binding modes of compounds with bacterial β‐GUS. Binding free energy decomposition revealed that the compounds formed strong interactions with E413 in catalytic trail from primary monomer and F365′ on the bacterial loop from the other monomer of bacterial β‐GUS, explaining the selectivity against mammalian β‐GUS. The old drugs identified here may be used as bacterial β‐GUS inhibitors for CID or other bacterial β‐GUS‐related disorders.
Authoritarian Neoliberalism, Radical Conservatism and Social Policy within the European Union: Croatia, Hungary and Poland
Authors: Stubbs Paul , Lendvai‐Bainton Noémi 
Published: December 2019

ABSTRACTExploring political and social policy developments in Croatia, Hungary and Poland, three EU member states, this article addresses the hegemonic position of authoritarianism, populism, conservatism and neoliberalism, albeit articulated differently in each state. All three countries are marked by modes of governmentality that combine heteronormative familialism, repatriarchialization, nationalism, ethnicized demographic renewal and anti‐immigrant sentiments. In each, a kind of layered social divestment is occurring, delivering a radical new vision of social reproduction and fundamental differentiations in terms of access to social citizenship between those seen as ‘deserving’ of support and those who are not, who are increasingly subjected to disciplinary measures. Although the degree of welfare retrenchment varies across the cases, the radical nature of restructuring, breaking down traditional notions of left and right on welfare, is suggestive of longer‐term restructurings not reliant on individual politicians or parties.
Sweet dreams or bitter nightmare: a narrative review of 25 years of research on the role of sleep in diabetes and the contributions of behavioural science
Authors: Nefs G.M. , Bazelmans E. , Donga E. , Tack C. J. , de Galan B. E. 
Published: December 2019

AbstractThe aim of this review was to provide an overview of developments, clinical implications and gaps in knowledge regarding the relationship between diabetes and sleep over the past 25 years, with special focus on contributions from the behavioural sciences. Multiple prospective observational and experimental studies have shown a link between suboptimal sleep and impaired glucose tolerance, decreased insulin sensitivity and the development of type 2 diabetes. While prevalence rates of suboptimal sleep vary widely according to definition, assessment and sample, suboptimal subjective sleep quality appears to be a common reality for one‐third of people with type 1 diabetes and over half of people with type 2 diabetes. Both physiological and psychosocial factors may impair sleep in these groups. In turn, suboptimal sleep can negatively affect glycaemic outcomes directly or indirectly via suboptimal daytime functioning (energy, mood, cognition) and self‐care behaviours. Technological devices supporting diabetes self‐care may have both negative and positive effects. Diabetes and its treatment also affect the sleep of significant others. Research on the merits of interventions aimed at improving sleep for people with diabetes is in its infancy. Diabetes and sleep appear to be reciprocally related. Discussion of sleep deserves a central place in regular diabetes care. Multi‐day, multi‐method studies may shed more light on the complex relationship between sleep and diabetes at an individual level. Intervention studies are warranted to examine the potential of sleep interventions in improving outcomes for people with diabetes.
EEG spectral power, but not theta/beta ratio, is a neuromarker for adult ADHD
Authors: Kiiski Hanni , Bennett Marc , Rueda‐Delgado Laura M. , Farina Francesca R. , Knight Rachel , Boyle Rory , Roddy Darren , Grogan Katie , Bramham Jessica , Kelly Clare , Whelan Robert 
Published: December 2019

AbstractAdults with attention‐deficit/hyperactivity disorder (ADHD) have been described as having altered resting‐state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behaviour (mediational endophenotypes). Resting‐state eyes‐open and eyes‐closed EEG was measured from 38 adults with ADHD, 45 first‐degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1–45 Hz) and TBR could classify participants into ADHD, first‐degree relatives and/or control groups. Random‐label permutation was used to quantify any bias in the analysis. Eyes‐open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = 0.71–0.77). The best predictors of ADHD status were increased power in delta, theta and low‐alpha over centro‐parietal regions, and in frontal low‐beta and parietal mid‐beta. TBR did not successfully classify ADHD status. Elevated eyes‐open power in delta, theta, low‐alpha and low‐beta distinguished first‐degree relatives from controls (area under receiver operating characteristic = 0.68–0.72), suggesting that these features may be a mediational endophenotype for adult ADHD. Resting‐state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.