bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race, Ethnicity, and Clinical Features of Alcohol Use Disorder Among US Military Veterans: Results From the National Health and Resilience in Veterans Study
Authors: Carr Meagan M. , Potenza Marc N. , Serowik Kristin L. , Pietrzak Robert H. 
Published: June 2020

Background and ObjectivesAlcohol use disorder (AUD) is highly prevalent in US military veterans, though little is known about whether the psychiatric comorbidities and functional outcomes (ie, clinical features) of AUD differ across race/ethnic groups. We aimed to identify differences in the clinical features of veterans with AUD by race/ethnicity.MethodsIn a sample of veterans with AUD (n = 1212) from the nationally representative National Health and Resilience in Veterans Study, we compared the clinical features associated with AUD across racial/ethnic groups using analysis of covariance and logistic regression.ResultsBlack veterans (n = 60, 34.0%) were less likely to screen positive for lifetime AUD compared with white (n = 1099, 42.7%) and Hispanic (n = 53, 41.5%) veterans. Among those with lifetime AUD, Hispanic veterans were more likely than white veterans to have lifetime and current mood or anxiety disorders (adjusted odds ratio range [AORR] = 2.21‐2.52, P < .05). Black veterans were more likely than white veterans to have current mood and anxiety disorders (AORR = 2.01‐3.07, P < .05). Hispanic veterans reported poorer functioning and quality of life than white and black veterans (Cohen's d range = 0.12‐0.37, P < .05).Discussion and ConclusionsBlack and Hispanic veterans with lifetime AUD may experience a higher disease burden relative to white veterans. Results underscore the importance of race/ethnicity‐sensitive assessment, monitoring, and treatment of AUD for veterans.Scientific SignificanceThis is the first known study to examine differences by race/ethnicity in the clinical features of Veterans with AUD in a nationally representative sample. Findings suggest higher disease burden for racial/ethnic minority veterans. (Am J Addict 2021;30:26–33)
Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone
Authors: Antoine Denis , Huhn Andrew S. , Strain Eric C. , Turner Gavin , Jardot Jasmyne , Hammond Alexis S. , Dunn Kelly E. 
Published: June 2020

Background and ObjectivesIndividuals exposed to fentanyl are at risk of precipitated withdrawal using typical buprenorphine/naloxone induction procedures.MethodsThis case series describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl.ResultsBuprenorphine‐precipitated withdrawal was observed in two individuals who completed a conventional buprenorphine/naloxone induction strategy. Two more individuals completed a revised buprenorphine/naloxone induction strategy that did not precipitate withdrawal.Discussion and ConclusionUsing multiple 2 mg doses of buprenorphine/naloxone in patients already in mild/moderate withdrawal improved outcomes.Scientific SignificancePersons who use illicit fentanyl might be less likely to experience precipitated withdrawal from this revised buprenorphine/naloxone induction strategy. (Am J Addict 2021;30:83–87)
Renal immune‐related adverse events of immune checkpoint inhibitor
Authors: Hu Rongrong , Chen Minjiang , Xu Yan , Wang Mengzhao , Zheng Ke , Li Xuemei 
Published: June 2020

AbstractThe status of immune checkpoint inhibitors (ICPIs) is raising in the treatment of malignancy for their effectiveness. The ICPIs therapy takes the risk of off‐target toxicity because of immune system overactivation, including renal toxicity. It was declared that the renal toxicity was rare. However, with the increasing experience of ICPIs therapy, the renal immune‐relate adverse events of ICPIs were reported more and their management was launching an enthusiastic discussion nowadays. In this review, we focused on the mechanism of ICPIs related renal irAEs (immune‐related adverse events), the clinical and pathological manifestation of different forms of renal injury, and management strategies when the renal irAEs happened. Good management of irAEs might need help from Multi‐Disciplinary Treatment and could promote a better clinical practice on ICPIs.
Decidual memory T‐cell subsets and memory T‐cell stimulatory cytokines in early‐ and late‐onset preeclampsia
Authors: Kieffer Tom E. C. , Laskewitz Anne , Vledder Annegé , Scherjon Sicco A. , Faas Marijke M. , Prins Jelmer R. 
Published: June 2020

AbstractProblemPreeclampsia is a major cause of fetal and maternal mortality and morbidity. Disturbed fetal‐maternal immune tolerance, and therewith memory T cells, might be involved in its etiology. This study aims to give insight into memory T‐cell populations and its associated cytokines in the decidual layers in early‐onset preeclampsia (EO‐PE) and late‐onset preeclampsia (LO‐PE).Method of StudyLymphocytes were isolated from the decidua parietalis and basalis from EO‐PE (n = 6), LO‐PE (n = 8) and healthy (n = 15) pregnancies. CD4+ and CD8+ central‐ (CCR7+), effector‐ (CCR7−), tissue resident‐ (CD103+), and regulatory‐ (Foxp3+) memory cell (CD45RO+) populations and their activation status (CD69+) were analyzed using flow cytometry. qRT‐PCR analysis was performed on decidua parietalis and basalis biopsies to detect mRNA expression of interferon‐gamma, interleukin‐1B, IL2, IL6, IL7, IL8, IL10, IL15, and IL23.ResultsCD4+ central‐memory (CM) cell proportions were lower in the decidua parietalis in LO‐PE (P < .0001) and EO‐PE (P < .01) compared to healthy pregnancies. CD8+ memory (P < .05) and CD8+ CM (P < .01) cell proportions were also lower in the decidua parietalis in EO‐PE compared to healthy pregnancies. This was accompanied by higher IL15 (P < .05) and IL23 (P < .05) and lower IL7 (P < .05) mRNA expression in decidua basalis biopsies from EO‐PE compared to healthy pregnancies, analyzed by qPCR.ConclusionIn conclusion, decidual memory T‐cell proportions, their activation status, and associated cytokines are altered in preeclampsia and might therefore be involved in fetal‐maternal immune tolerance and the pathophysiology of preeclampsia.
Comparison of skin autofluorescence, a marker of tissue advanced glycation end‐products in the fistula and non‐fistula arms of patients treated by hemodialysis
Authors: Tangwonglert Theerasak , Vareesangthip Kornchanok , Vongsanim Surachet , Davenport Andrew 
Published: June 2020

AbstractAdvanced glycosylation end‐products (AGEs) are reported to be a risk factor for cardiovascular mortality in hemodialysis (HD) patients. As serum AGEs can change with dialysis, measurement of AGEs deposited in the skin by autofluorescence (SAF) is now a recognized method of measuring AGEs. An arteriovenous fistula (AVF) is the preferred way to access blood in HD patients, and as the creation of an AVF changes blood flow distribution in the arm, we wished to determine whether this affected SAF deposition in the skin. SAF was measured using the AGE reader, which directs ultraviolet light at an intensity range of 300‐420 nm (peak 370 nm) in the arms of HD patients dialyzing with an AVF. We measured SAF in 267 patients, 60.3% male, 46.1% diabetic, median duration of dialysis 34.7 (15.1‐64.2) months with AVF. The median SAF was lower in the AVF arm (median 3.4 (2.9‐4.2) vs. 3.7 (3.2‐4.5) AU, P < .001), and for the 160 patients with an upper arm AVF (3.5 (2.9‐4.3) vs. 3.8 (3.2‐4.5) AU, P < .001), but not for the 107 patients dialyzing with a forearm AVF ((3.4 (2.8‐4.2) vs. 3.6 (3.0‐4.5) AU, P = .085). Blood flow was greater for upper arm AVF compared to forearm AVFs (1190 (770‐1960) vs. (930 (653‐1250) mL/min, P = .007), but there was no association between blood flow and SAF (P > .05). AVF alters blood flow in the arm, and we found that SAF measurements were lower in the arm with AVF. We suggest that SAF measurements are made in the non‐AVF arm.
Retinal vessel oximetry in children with inherited retinal diseases
Authors: della Volpe Waizel Maria , Scholl Hendrik P. N. , Valmaggia Christophe , Todorova Margarita G. 
Published: June 2020

AbstractBackgroundRetinal vessel oximetry (RO) has been used to show altered metabolic function in patients with inherited retinal diseases (IRDs). The aim of this study was to investigate RO parameters of children with IRDs and presumed IRD carriers (pIRDc) and to compare them to controls.MethodsIn this cross‐sectional cohort study, 142 eyes from 71 Caucasian subjects were included: 40 eyes with IRDs, 26 eyes with pIRDc and 76 control eyes. The oxygen saturation was measured with the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). Mean oxygen saturations in the peripapillary retinal arterioles (A‐SO2; %) and venules (V‐SO2; %) were estimated, and their difference (A‐V SO2; %) was calculated. In addition, we evaluated the mean diameter in all major retinal arterioles (D‐A; μm) and venules (D‐V; μm). anova‐based linear mixed‐effects models were calculated with SPSS®.ResultsIn general, children suffering from IRDs differed from controls when the A‐SO2 and A‐V SO2 were taken into account: both the A‐SO2 and the A‐V SO2 were significantly increased (p = 0.012). In subgroup analyses, children suffering from rod–cone dystrophy (RCD) presented an A‐SO2 increase (99.12 ± 8.24%) when compared to controls (91.33 ± 10.34%, p = 0.014) and pIRDc (92.37 ± 6.57%, p = 0.065). For V‐SO2 significant changes in RCD (67.42 ± 9.19%) were found in comparison with controls (58.24 ± 11.74%, p < 0.041), pIRDc (56.67 ± 7.16%, p = 0.007), cone–rod dystrophies (CRD, 52.17 ± 5.32%, p < 0.001) and inherited macular dystrophies (IMD, 55.74 ± 6.96%, p = 0.004), In addition, A‐V SO2 was decreased in RCD (31.69 ± 3.92%) when measured against CRD (41.9 ± 8.87%, p = 0.017) or IMD (39.52 ± 8.95%, p = 0.059).ConclusionIn general, we found that children with IRDs presented early metabolic changes. Within IRDs, children with RCD showed more affected metabolic changes. Thus, RO may support early screening to rule out IRDs in children, and more precisely may help to differentiate those suffering from RCD.
A virtue ethics critique of ethical dimensions of behavioral economics: Comments from a behavioral economist
Authors: Livingston Jeffrey A. 
Published: June 2020

AbstractIn “A Virtue Ethics Critique of Ethical Dimensions of Behavioral Economics,” Professor Daryl Koehn criticizes the field of behavioral economics. She argues that behavioral economists ignore many important factors that affect how people make decisions, that their results are derived from experiments where subjects make choices in overly restrictive, artificial, and thin contexts that do not capture the richness of reality, and that the approach brings up psychological motivations that affect behavior in a piecemeal, ad hoc way that does not capture the overall tapestry of the factors that influence the choices that we make. In this comment, I offer responses to many of these criticisms, and note where I think we have common ground.
Paracetamol‐induced metabolic and cardiovascular changes are prevented by exercise training
Authors: Ayres Júlio Cesar , Porto Hellen Karine Paes , de Andrade Daniela Medeiros Lobo , Junior José Britto , Ribeiro Marco Tulio Lacerda , Rocha Matheus Lavorenti 
Published: June 2020

AbstractParacetamol (PAR) is the most frequently consumed non‐prescription drug, yet it is well known to induce toxicity. Here, we have evaluated the effects of exercise training on vascular dysfunction induced by PAR. Rats were distributed among four groups: (a) Sedentary; (b) Exercise; (c) Sedentary+PAR; and (d) Exercise+PAR. The exercise comprised swimming 50 min/d, 5 d/wk for 6 weeks (+PAR in the last 2 weeks, at 400 mg/kg/d/p.o.). After killing, the rats' blood and aortas were collected for biochemical analysis of hepatic transaminases, TBARs reaction, glutathione, glutathione reductase, SOD, and catalase. In vitro vascular relaxation was measured using acetylcholine and sodium nitroprusside in the presence or absence of tiron (an antioxidant). Vascular protein expression (eNOS and sGC) also were analysed. Increased transaminases after PAR treatment were found to be reduced by exercise. Vasodilation was impaired by PAR only in the sedentary group. Exercise prevented alterations in lipoperoxidation and glutathione levels after PAR exposure. Glutaathione reductase and SOD also were increased by PAR but were normalized in the exercised group. Catalase activity and protein expressions did not change in any group. PAR treatment caused impairment in both vasodilation and redox balance; however, exercise training prevented the vascular and redox system dysfunction induced by PAR treatment.
Heterogeneity of cancer‐associated fibroblasts: Opportunities for precision medicine
Authors: Kanzaki Ryu , Pietras Kristian 
Published: June 2020

AbstractDespite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor. The conventional tumor–cell‐centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial. Among cells within the TME, cancer‐associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy. However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF‐targeted therapies. In this context, application of newly developed approaches to single‐cell analysis has already made an impact on our understanding of the heterogeneity of CAFs. Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets.
Synthesis of celastrol derivatives as potential non‐nucleoside hepatitis B virus inhibitors
Authors: Zhang He , Lu Gongxi 
Published: June 2020

AbstractA series of para‐quinone methide (pQM) moiety and C‐20‐ modified derivatives of celastrol were synthesized and evaluated for their inhibitory effect on the secretion of HBsAg and HBeAg as well as the inhibitory effect against HBV DNA replication. The results suggested that amidation of C‐20 carboxylic group could generate derivatives with good anti‐HBV profile, among them compound 14 showed the best inhibitory activity on the secretion of HBsAg (IC50 = 11.9 µμ) and HBeAg (IC50 = 13.1 µμ) with SI of 3.3 and 3.0, respectively. In addition, 14 also showed potent inhibitory effect against HBV DNA replication (48.5 ± 15.1%, 25 µM). This is, to our knowledge, the first report of celastrol derivatives as potential non‐nucleoside HBV inhibitors.
The role of glial cell line‐derived neurotrophic factor family member artemin in neurological disorders and cancers
Authors: Zhu Sipin , Li Yihe , Bennett Samuel , Chen Junhao , Weng Isabel Ziwai , Huang Lin , Xu Huazi , Xu Jiake 
Published: June 2020

AbstractArtemin (ARTN) is a member of the glial cell line‐derived neurotrophic factor (GDNF) family ligands (GFLs), which encompasses family members, GDNF, neurturin (NRTN) and persephin (PSPN). ARTN is also referred to as Enovin or Neublastin, and bears structural characteristics of the TGF‐β superfamily. ARTN contains a dibasic cleavage site (RXXR) that is predicted to be cleaved by furin to yield a carboxy‐terminal 113 amino acid mature form. ARTN binds preferentially to receptor GFRα3, coupled to a receptor tyrosine kinase RET, forming a signalling complex for the regulation of intracellular pathways that affect diverse outcomes of nervous system development and homoeostasis. Standard signalling cascades activated by GFLs via RET include the phosphorylation of mitogen‐activated protein kinase or MAPK (p‐ERK, p‐p38 and p‐JNK), PI3K‐AKT and Src. Neural cell adhesion molecule (NCAM) is an alternative signalling receptor for ARTN in the presence of GFRα1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan‐3 and mediates non‐RET signalling via activation of Src kinases. This review discusses the role of ARTN in spinal cord injury, neuropathic pain and other neurological disorders. Additionally, ARTN plays a role in non‐neuron tissues, such as the formation of Peyer's patch‐like structures in the lymphoid tissue of the gut. The emerging role of ARTN in cancers and therapeutic resistance to cancers is also explored. Further research is necessary to determine the function of ARTN in a tissue‐specific manner, including its signalling mechanisms, in order to improve the therapeutic potential of ARTN in human diseases.
Treatment of borderline infiltrates with minimal inflammation in kidney transplant recipients has no effect on allograft or patient outcomes
Authors: Dale Leigh‐Anne , Brennan Corey , Batal Ibrahim , Morris Heather , Jain Namrata G. , Valeri Anthony , Husain Syed A. , King Kristen , Tsapepas Demetra , Cohen David , Mohan Sumit 
Published: June 2020

AbstractIn 2005, the Banff committee expanded the “borderline changes” category to include lesions with minimal (<10%) inflammation: “i0” borderline infiltrates. Clinical significance and optimal treatment of i0 borderline infiltrates are not known. Data suggest that i0 borderline infiltrates may have a more favorable prognosis than borderline infiltrates with higher grades of interstitial inflammation. In this single‐center, retrospective, observational study, we assessed 90 renal transplant recipients with i0 borderline infiltrates on biopsies indicated for graft dysfunction. We studied the impact of treatment with corticosteroids on allograft function, allograft survival, and patient survival. We found no differences between treated and untreated groups with respect to eGFR at 4 weeks and 6 months after biopsy. Follow‐up biopsies, available in 67% of patients, were negative for rejection in almost half of all cases, regardless of treatment status. The frequencies of persistent borderline infiltrates (38%) and higher‐grade T cell–mediated rejection (1A or greater, 14%) on follow‐up biopsies were similar between the two groups. There were no differences in rejection‐free allograft survival, death‐censored graft failure, or patient mortality among treated vs non‐treated i0 borderline patients. Our findings suggest that the natural history of i0 borderline infiltrates, in relatively low immunologic risk patients, is not affected by corticosteroid treatment.
Exenatide extended release in patients with type 1 diabetes with and without residual insulin production
Authors: Herold Kevan C. , Reynolds Jesse , Dziura James , Baidal David , Gaglia Jason , Gitelman Stephen E. , Gottlieb Peter A. , Marks Jennifer , Philipson Louis H. , Pop‐Busui Rodica , Weinstock Ruth S. 
Published: June 2020

AbstractAimsTo test whether a long‐acting GLP‐1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo‐controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C‐peptide. Seventy‐nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C‐peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C‐peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short‐term benefits in some individuals with T1D who are overweight or who have detectable levels of C‐peptide, but short‐term improvements were not sustained.
COVID‐19 and thalassaemia: A position statement of the Thalassaemia International Federation
Authors: Farmakis Dimitrios , Giakoumis Anastasios , Cannon Lily , Angastiniotis Michael , Eleftheriou Androulla 
Published: June 2020

AbstractObjectivesMany patients with haemoglobinopathies, including thalassaemia and sickle cell disease, are at increased risk of developing severe complications from the coronavirus disease 2019 (COVID‐19). Although epidemiologic evidence concerning the novel coronavirus (SARS‐CoV‐2) infection in these patients is currently lacking, the COVID‐19 pandemic represents a significant challenge for haemoglobinopathy patients, their families and their attending physicians.MethodsThe present statement summarizes the key challenges concerning the management of haemoglobinopathies, with particular focus on patients with either transfusion‐dependent or non‐transfusion‐dependent thalassaemia, identifies the gaps in knowledge and suggests measures and strategies to deal with the pandemic, based on available evidence and expert opinions. Key areas covered include patients’ risk level, adaptation of haemoglobinopathy care, safety of blood transfusions, blood supply challenges, and lifestyle and nutritional considerations.ConclusionsThe proposed measures and strategies may be useful as a blueprint for other disorders which require regular hospital visits, as well as for the timely adaptation of patient care during similar future pandemics.
Rousseau's three revolutions
Authors: Hanley Ryan Patrick 
Published: June 2020

AbstractRousseau's relation to the French Revolution – and in particular his status as the Revolution's precursor or predictor or progenitor – has been often examined. Yet almost no sustained attention has been given to what is arguably Rousseau's most significant and explicit statement on revolution and its role in civilization's development. This paper calls attention to this statement and argues for its key significance on three fronts: first, for how it organizes Rousseau's conjectural history of civilization in the second Discourse; second, for the insight it offers into the processes of Rousseau's pre‐Hegelian philosophy of history; and third, for the normative political implications of its standard for measuring the relative progress of inequality in a given society at a given time.
Selection on ultrasonic call rate in neonatal rats affects low frequency, but not ultrasonic, vocalizations in adults
Authors: Lesch Raffaela , Orozco Andrea , Shilling Margaret , Zimmerberg Betty , Fitch W. Tecumseh 
Published: June 2020

AbstractIn this experiment, we studied a rodent model selected over 57 generations for high or low rates of ultrasonic vocalizations (USVs) during maternal separation as pups. We investigated the influence of this breeding on the adult animals’ subsequent vocal output, comparing acoustic variables across developmental stages. We hypothesized that selection on pup USV rate would impact adult USV production without affecting lower frequency calls. Contrary to this hypothesis, we found neither number of USV calls or other acoustic variables to differ among selected adult lines. Instead, we found that pup USV selection mainly affected adults’ low‐frequency (human‐audible) calls. Furthermore, low‐frequency vocalizations did not fully fit a predicted correlation between body weight and fundamental frequency: high line males, although the heaviest on average, did not produce the lowest fundamental frequencies. Our findings suggest that selection for early ultrasonic vocal behaviour pleiotropically results in changes in anatomical production mechanisms and/or neural control affecting low‐frequency calls.