bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic potential of opioid receptor heteromers in chronic pain and associated comorbidities
Authors: Gaborit Marion , Massotte Dominique 
Published: December 2021

Chronic pain affects 20% to 45% of the global population and is often associated with the development of anxio‐depressive disorders. Treatment of this debilitating condition remains particularly challenging with opioids prescribed to alleviate moderate to severe pain. However, despite strong antinociceptive properties, numerous adverse effects limit opioid use in the clinic. Moreover, opioid misuse and abuse have become a major health concern worldwide. This prompted efforts to design original strategies that would efficiently and safely relieve pain. Targeting of opioid receptor heteromers is one of these. This review summarizes our current knowledge on the role of heteromers involving opioid receptors in the context of chronic pain and anxio‐depressive comorbidities. It also examines how heteromerization in native tissue affects ligand binding, receptor signalling and trafficking properties. Finally, the therapeutic potential of ligands designed to specifically target opioid receptor heteromers is considered.LINKED ARTICLESThis article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples
Authors: Di Wang , Fan Wenhua , Wu Fan , Shi Zhongfang , Wang Zhiliang , Yu Mingchen , Zhai You , Chang Yuanhao , Pan Changqing , Li Guanzhang , Kahlert Ulf Dietrich , Zhang Wei 
Published: December 2021

AbstractBackgroundGlioblastoma is a paradigm of cancer‐associated immunosuppression, limiting the effects of immunotherapeutic strategies. Thus, identifying the molecular mechanisms underlying immune surveillance evasion is critical. Recently, the preferential expression of inhibitory natural killer (NK) cell receptor CD161 on glioma‐infiltrating cytotoxic T cells was identified. Focusing on the molecularly annotated, large‐scale clinical samples from different ethnic origins, the data presented here provide evidence of this immune modulator's essential roles in brain tumor biology.MethodsRetrospective RNA‐seq data analysis was conducted in a cohort of 313 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 603 patients in The Cancer Genome Atlas (TCGA) database. In addition, single‐cell sequencing data from seven surgical specimens of glioblastoma patients and a model in which patient‐derived glioma stem cells were cocultured with peripheral lymphocytes, were used to analyze the molecular evolution process during gliomagenesis.ResultsCD161 was enriched in high‐grade gliomas and isocitrate dehydrogenase (IDH)‐wildtype glioma. CD161 acted as a potential biomarker for the mesenchymal subtype of glioma and an independent prognostic factor for the overall survival (OS) of patients with glioma. In addition, CD161 played an essential role in inhibiting the cytotoxicity of T cells in glioma patients. During the process of gliomagenesis, the expression of CD161 on different lymphocytes dynamically evolved.ConclusionThe expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Thus, CD161 is a promising novel target for immunotherapeutic strategies in glioma treatment.
Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF‐1 levels, while improving height in patients small for gestational age A long‐term observational study
Authors: López‐Siguero Juan P. , Martínez‐Aedo Maria J. , Bermúdez de la Vega Jose Antonio , Bosch‐Muñoz Jordi , Lechuga‐Sancho Alfonso M. , Villalobos Triana ,   SGA Study Investigator Collaborative Group
Published: December 2021

AbstractObjectiveIn children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long‐term (10 years) effect of GH to SGA‐children on IR and safety during treatment.DesignThis was a multicenter observational study.Patients: SGA‐children who received GH treatment in Spain (stratified by Tanner‐stage and age at GH onset [two groups: ≤6 years old or >6 years old]).Measurements: The analysed variables (yearly measures) included auxologic, metabolic (insulin‐like growth factor‐1 (IGF‐1), height velocity [HV], weight and homeostatic model assessment‐IR [HOMA‐IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005–2007).ResultsA total of 389 SGA children (369 Tanner‐I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF‐1 (standard deviation score [SDS]) and HOMA‐IR values tended to increase until the sixth year of GH‐treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: −3.0; tenth year: −1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39).ConclusionsHOMA‐IR values increased significantly in SGA‐children during the first year of GH‐treatment, remained stable and were within normal ranges in all cases. Our 10‐year data suggests that long‐term GH treatment does not promote IR and is well‐tolerated, safe and effective.
A survey on the psychological impact and access to health care of thyroid patients during the first SARS‐COV‐2 lockdown
Authors: Pavlatou Maria G. , Žarković Miloš , Hegedüs Laszlo , Priestley Julia , McMullan Cheryl , Perros Petros 
Published: December 2021

AbstractObjectiveInformation on the impact of SARS‐COV‐2 on the daily life of thyroid patients during lockdown is sparse. The main objective was explorative, focusing on how SARS‐COV‐2 affected thyroid patients.DesignCross‐sectional, questionnaire‐based, using an online platform.PatientsPatients >18 years with a history of thyroid disease.MeasurementsDemographic data, psychological impact of SARS‐COV‐2, medical care during the pandemic.ResultsValid responses were received from 609 responders. The median age was 50 years, 94% were female and 98.5% were UK residents. The commonest diagnosis was primary hypothyroidism (52.2%). Negative psychological effects following the lockdown were reported by 45.6%–58.7%. Cancellations of appointments with thyroid specialists were reported by 43.8%, although cancellations of thyroid investigations and treatments were relatively infrequent (12.9%–14.1%). Overall satisfaction rates for thyroid services were low (satisfaction score 40.1–42.8 out of 100), but nearly 80% were satisfied with remote consultations. Responder ratings of online information sources about SARS‐COV‐2 and thyroid diseases were lowest for government sites. Unmet needs during lockdown were: more remote access to thyroid specialists, more online information in ‘plain English’, and psychological support. In multivariate analyses, younger age, female gender, history of depression, hyperthyroidism, not having contracted SARS‐COV‐2 and multiple comorbidities were risk factors for a negative psychological impact of lockdown.ConclusionsThis survey identified a significant negative impact of SARS‐COV‐2 and lockdown on psychological wellbeing, particularly in some groups of patients defined by demographic factors, history of hyperthyroidism and comorbidities. Low satisfaction with healthcare services among thyroid patients was noted, but remote consultations were rated favourably.
Immersive Analytics with Abstract 3D Visualizations: A Survey
Authors: Kraus Matthias , Fuchs Johannes , Sommer Björn , Klein Karsten , Engelke Ulrich , Keim Daniel , Schreiber Falk 
Published: December 2021

AbstractAfter a long period of scepticism, more and more publications describe basic research but also practical approaches to how abstract data can be presented in immersive environments for effective and efficient data understanding. Central aspects of this important research question in immersive analytics research are concerned with the use of 3D for visualization, the embedding in the immersive space, the combination with spatial data, suitable interaction paradigms and the evaluation of use cases. We provide a characterization that facilitates the comparison and categorization of published works and present a survey of publications that gives an overview of the state of the art, current trends, and gaps and challenges in current research.
Anonymous living liver donor perspectives on the role of family in their donation experience
Authors: Humar Sapna , Jung Judy , Krause Sandra , Selzner Nazia , Abbey Susan 
Published: December 2021

AbstractAnonymous living organ donation is an understudied but rapidly expanding sector in organ transplantation, in which donors choose to donate anonymously to a recipient in need. The family members and close support network of living donors often play a crucial role in the donation process, and their influence likely has a large impact on the decision to donate as well as the donor's physical and psychosocial state. However, there is limited data examining the impact donor families have on the anonymous donor, and in turn, the impact donation has on donors’ families. To assess this, we analyzed a semi‐structured qualitative interview on living donor experiences with 26 anonymous living liver donors for common themes concerning donor families. Responses surrounding donor families were grouped into three major categories: (1) family reactions to donation, ranging from (a) pride/support, (b) fear/worry, and (c) jealousy/anger; (2) the impact of donation on donor‐family relationships, including (a) positive impacts, (b) negative impacts, (c) a positive ripple effect; (3) gaps in institutional support for donor families. This study provides unique information on anonymous living liver donor perceptions related to their families and will help improve existing programs to accommodate donor family needs and cater to donor relationships.
Do post‐quitting experiences predict smoking relapse among former smokers in Australia and the United Kingdom? Findings from the International Tobacco Control Surveys
Authors: Gorniak Bradley , Yong Hua‐Hie , Borland Ron , Cummings K. Michael , Thrasher James F. , McNeill Ann , Hyland Andrew , Fong Geoffrey T. 
Published: December 2021

AbstractIntroductionMany smokers attempt to stop smoking every year, but the vast majority of quit attempts fail. This study examined prospectively the association between post‐quitting experiences and smoking relapse among ex‐smokers in Australia and the United Kingdom.MethodsData came from 584 adult ex‐smokers from Australia and the United Kingdom who participated in Wave 9 of the International Tobacco Control Four Country Survey and successfully followed up a year later (Wave 10). Binary logistic regression was used to examine whether baseline post‐quitting experiences predicted relapse back to smoking at follow‐up.ResultsEx‐smokers who perceived their stress coping ability had gotten worse since quitting were more likely to relapse back to smoking compared to their counterparts who reported no change (odds ratio = 5.77, 95% confidence interval = 1.64, 20.31, P < 0.01). Ex‐smokers who reported their homes had become fresher and cleaner post quitting were less likely to relapse compared to those who did not notice any change (odds ratio = 0.34, 95% confidence interval = 0.13, 0.93, P < 0.05). Perceived changes in life enjoyment, negative affect control, social confidence, work performance, leisure time and financial situation did not independently predict relapse. No country differences were found.Discussion and ConclusionsThe study showed that ex‐smokers' relapse risk was elevated if they perceived any negative impact of quitting on their stress coping whereas relapse risk was reduced if they perceived any positive impact of quitting on the home (e.g. fresher and cleaner). Helping ex‐smokers to develop alternative stress coping strategies and highlighting the positive impacts of quitting smoking on the homes may help protect against smoking relapse.
Melanocortin‐4 receptor complexity in energy homeostasis,obesity and drug development strategies
Authors: Fatima Munazza Tamkeen , Ahmed Ikhlak , Fakhro Khalid Adnan , Akil Ammira Sarah Al‐Shabeeb 
Published: December 2021

AbstractThe melanocortin‐4 receptor (MC4R) has been critically investigated for the past two decades, and novel findings regarding MC4R signalling and its potential exploitation in weight loss therapy have lately been emphasized. An association between MC4R and obesity is well established, with disease‐causing mutations affecting 1% to 6% of obese patients. More than 200 MC4R variants have been reported, although conflicting results as to their effects have been found in different cohorts. Most notably, some MC4R gain‐of‐function variants seem to rescue obesity and related complications via specific pathways such as beta‐arrestin (ß‐arrestin) recruitment. Broadly speaking, however, dysfunctional MC4R dysregulates satiety and induces hyperphagia. The picture at the mechanistic level is complicated as, in addition to the canonical G stimulatory pathway, the ß‐arrestin signalling pathway and ions (particularly calcium) seem to interact with MC4R signalling to contribute to or alleviate obesity pathogenesis. Thus, the overall complexity of the MC4R signalling spectra has broadened considerably, indicating there is great potential for the development of new drugs to manage obesity and its related complications. Alpha‐melanocyte‐stimulating hormone is the major endogenous MC4R agonist, but structure‐based ligand discovery studies have identified possible superior and selective agonists that can improve MC4R function. However, some of these agonists characterized in vitro and in vivo confer adverse effects in patients, as demonstrated in clinical trials. In this review, we provide a comprehensive insight into the genetics, function and regulation of MC4R and its contribution to obesity. We also outline new approaches in drug development and emerging drug candidates to treat obesity.
Cavell's inheritance of Luther
Authors: Norris Andrew 
Published: December 2021

AbstractThe question of Martin Luther's influence on Stanley Cavell has been almost entirely neglected in the extensive scholarly literature on Cavell. Yet, Luther's name appears prominently and repeatedly in Cavell's initial discussions of his central concepts of acknowledgment and the truth of skepticism. Though the former is often taken to be an essentially interpersonal matter, I argue that it concerns first and foremost that aspect of the world Kant names theDing an sich, and that Cavell's understanding of this follows Luther's conception of our proper relation to God. On this basis, I then argue that Luther's “baptismal life” contains most of the essential elements of Cavell's Romanticism and what he will later term Emersonian Perfectionism. This perfectionism is in effect an “alternative secularization” of Luther's Reformation. As with Kierkegaard, on whom Cavell also draws heavily, though Luther appears less and less in Cavell's work afterThe Claim of Reason, his initial influence on Cavell's central ideas is decisive.
The effect of polygenic risk on white matter microstructural degeneration in Parkinson's disease: A longitudinal Diffusion Tensor Imaging study
Authors: Gu Luyan , Guan Xiaojun , Gao Ting , Zhou Cheng , Yang Wenyi , Lv Dayao , Wu Jingjing , Fang Yi , Guo Tao , Song Zhe , Xu Xiaojun , Tian Jun , Yin Xinzhen , Zhang Minming , Zhang Baorong , Pu Jiali , Yan Yaping 
Published: December 2021

AbstractBackground and purposeThis study was undertaken to investigate the effect of genetic risk on whole brain white matter (WM) integrity in patients with Parkinson disease (PD).MethodsData were acquired from the Parkinson's Progression Markers Initiative (PPMI) database. Polygenic load was estimated by calculating weighted polygenic risk scores (PRS) using (i) all available 26 PD‐risk single nucleotide polymorphisms (SNPs) (PRS1) and (ii) 23 SNPs with minor allele frequency (MAF) > 0.05 (PRS2). According to the PRS2, and combined with clinical and diffusion tensor imaging (DTI) data over 3‐year follow‐up, 60 PD patients were screened and assigned to the low‐PRS group (n = 30) and high‐PRS group (n = 30) to investigate intergroup differences in clinical profiles and WM microstructure measured by DTI cross‐sectionally and longitudinally.RESULTSPRS were associated with younger age at onset in patients with PD (PRS1, Spearman ρ = −0.190, p = 0.003; PRS2, Spearman ρ = −0.189, p = 0.003). The high‐PRS group showed more extensive WM microstructural degeneration compared with the low‐PRS group, mainly involving the anterior thalamic radiation (AThR) and inferior fronto‐occipital fasciculus (IFOF) (p < 0.05). Furthermore, WM microstructural changes in AThR correlated with declining cognitive function (r = −0.401, p = 0.028) and increasing dopaminergic deficits in caudate (r = −0.405, p = 0.030).ConclusionsThese findings suggest that PD‐associated polygenic load aggravates the WM microstructural degeneration and these changes may lead to poor cognition with continuous dopamine depletion. This study provides advanced evidence that combined with a cumulative PRS and DTI methods may predict disease progression in PD patients.
Security or autonomy? A comparative analysis of work values and labor market policies in different European welfare states
Authors: Weiss Julia , Hörisch Felix 
Published: December 2021

AbstractThis paper analyzes whether and how work values differ between European Welfare states and change over time. We proceed in three steps: First, we show that—despite EU harmonization endeavors, for example, via the Europe 2020 strategy—work values still vary substantially between European countries and welfare regimes. Second, by analyzing data from the European Social Survey 2004 and 2010, we show how labor market policies, such as active and passive labor market policies, are associated with work values and how overall levels of work values changed over this period. Third, we discuss potential implications of the heterogeneity of work values for national as well as European labor market policy making. Altogether we are able to show that work values are substantially driven by the economic structure of a country and its labor market policy making.
Key Practitioner Message

Work values vary substantially between European countries and welfare regimes.

The change of work values is substantially driven by welfare state structures (both labor market policies implemented and industry share).

Both European and national labor market policy making has to account for these different work values to be successful.
Puzzling choices in hard times: Union ideologies of social concertation in the Great Recession
Authors: Tassinari Arianna , Donaghey Jimmy , Galetto Manuela 
Published: December 2021

AbstractUsing the cases of Ireland and Portugal during the post‐2008 Great Recession, we argue that unions' ideological formations around social concertation are central in aiding them to navigate their options about whether to engage in concessionary bargaining with government under crisis conditions. Building on Hyman's triangle of union identity, we show how an ideational perspective can complement interest‐based accounts of unions' strategies to explain their engagement with policymakers or their opposition in the macro‐management of the economy.
Customer satisfaction in the presence of imperfect knowledge of data
Authors: Ferreira Diogo Cunha , Soares Rodrigo , Pedro Maria Isabel , Marques Rui Cunha 
Published: December 2021

AbstractEnsuring customer satisfaction is at the top of any manager's agenda wishing to keep or raise profits. To do so, conducting regular surveys is quintessential. However, provided the large number of questions that typically constitute those surveys, resulting data are plagued with imperfect knowledge. Data from these surveys are typically expressed in ordinal scales. No mathematical operation like addition or multiplication is allowed in these cases. Recognizing the limitations of existing alternatives in the literature to model imperfect knowledge, this work proposes an alternative model for the study of satisfaction and its determinants. Our approach is based on merging the Stochastic Multicriteria Acceptability Analysis and the Multicriteria Satisfaction Analysis (model). We explore the potential of this approach and apply it to an empirical case related to hospitality.
Low‐temperature reactive sintering of carbon vacant high‐entropy carbide ceramics with in‐situ formed silicon carbide
Authors: Lin Guo‐Wei , Liu Ji‐Xuan , Qin Yuan , Zhang Guo‐Jun 
Published: December 2021

AbstractIt is thought that the sintering of high‐entropy (HE) ceramics is generally more difficult when compared to that of the corresponding single‐component ceramics. In this paper, we report a novel approach to densify the HE carbide ceramics at relatively low temperatures with a small amount of silicon. Reactive spark plasma sintering (SPS) was used to densify the ceramics using powders of HE carbide and silicon as starting materials. Dense ceramics can be obtained at 1600 ‐1700°C. X‐ray diffraction analysis reveals that only non‐stoichiometric HE carbide phase with carbon vacancy and SiC phase exist in the obtained ceramics. The in‐situ formed SiC phase inherits the morphology of the starting silicon powder owing to the slower diffusion of silicon atoms compared to that of the carbon atoms in HE carbide phase. The mechanical properties of the prepared ceramics were preliminarily studied.
Construction of a risk assessment model of cardiovascular disease in a rural Chinese hypertensive population based on lasso‐Cox analysis
Authors: Ouyang Nanxiang , Li Guangxiao , Wang Chang , Sun Yingxian 
Published: December 2021

AbstractMany assessments have been used to predict cardiovascular risks in the general population, but their applicability in patients with hypertension needs to be further evaluated. In the current study, a cardiovascular risk assessment model was constructed in a hypertensive population. This prospective cohort study was conducted with cardiovascular examinations in rural northeast China in 2012 and 2013, and followed up to collect cardiovascular events in 2015 and 2018. Data were derived from 4763 hypertensive patients who were free of cardiovascular disease (CVD) at baseline and completed follow‐up. After lasso regression was used to screen for risk factors of CVD at baseline, a multivariate Cox regression risk model was established and a nomogram was developed. The model was validated using an independent test set (one third of data not used for model building). Among 4763 patients, 354 (7.43%) had a cardiovascular event during a median follow‐up of 4.66 years. Nine risk factors were screened by lasso regression, including sex, age, current smoking, body mass index (BMI), history of transient ischemic attack (TIA), family history of hypertension, family history of stroke, physical labor intensity, and high low‐density lipoprotein cholesterol (LDL‐C). The c‐index of the CVD model was 0.707, and that of an updated model with baseline blood pressure was 0.732. In the validated cohort the respective c‐indexes were 0.665 and 0.714. An assessment model of CVD risk was established in a hypertensive population which may provide an original prevention strategy for hypertensive populations in rural China, and further reduce the CVD burden.