bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE
−/−
Mice
Authors: Wigren Maria , Rattik Sara , Yao Mattisson Ingrid , Tomas Lukas , Grönberg Caitriona , Söderberg Ingrid , Alm Ragnar , Sundius Lena , Ljungcrantz Irena , Björkbacka Harry , Fredrikson Gunilla Nordin , Nilsson Jan 
Published: April 2019

Background:

Hypercholesterolemic mice lacking factors required for activation of CD4
+
T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major histocompatibility complex class II (MHCII) leads to activation of proatherogenic Th1 cells. In this study, we wanted to determine the role of antigen presentation on MHCII in atherosclerosis development.

Methods:

Apolipoprotein E (ApoE
−/−
) mice deficient for MHCII (ApoE
−/−
MHCII
−/−
) were used to study the role of MHCII in atherosclerosis development.

Results:

Compared with ApoE
−/−
mice, ApoE
−/−
MHCII
−/−
mice had reduced levels of CD4
+
T cells, immunoglobulin G and M levels, and Th1 and Th2 cytokines in plasma. CD8
+
T cells were increased and regulatory T cells were reduced both in spleen and in lesions of ApoE
−/−
MHCII
−/−
mice. Decreased plasma levels of inflammatory cytokines in ApoE
−/−
MHCII
−/−
mice indicated reduced systemic inflammation. Despite this, ApoE
−/−
MHCII
−/−
mice had significantly more atherosclerosis as assessed by en face Oil Red O staining of the aorta (4.7±2.9% versus 1.9±1.3%;
P
<0.01) and cross-sectional area of subvalvular lesions (7.7±2.2×10
5
µm
2
versus 4.6±2.8×10
5
µm
2
;
P
<0.05). Cell transfer and blocking antibody studies suggested that loss of regulatory T cells is the most important cause of aggravated atherosclerosis in ApoE
−/−
MHCII
−/−
mice.

Conclusions:
Our observations demonstrate that antigen presentation on MHCII has important protective functions in atherosclerosis and that this is primarily the result of activation of regulatory T cells. These findings have implications for understanding the possible risks and benefits of immunosuppressive therapy in patients with cardiovascular disease.
Validation of Wall Enhancement as a New Imaging Biomarker of Unruptured Cerebral Aneurysm
Authors: Quan Kai , Song Jianping , Yang Zixiao , Wang Dongdong , An Qingzhu , Huang Lei , Liu Peixi , Li Peiliang , Tian Yanlong , Zhou Liangfu , Zhu Wei 
Published: April 2019

Background and Purpose—
High-resolution vessel wall magnetic resonance imaging is a promising technique for assessing wall structures of unruptured intracranial aneurysms (UIAs). However, the relationship between aneurysmal high-resolution vessel wall magnetic resonance imaging features and their histopathologic mechanism remains poorly understood.

Methods—
From February 2016 to February 2018, a total of 19 men and 28 women with 54 UIAs treated surgically were prospectively enrolled. The intraoperative observed gross pathology of the aneurysmal wall was compared with the enhancement features on high-resolution vessel wall magnetic resonance imaging. Specimens of the UIAs were harvested for histopathologic and immunohistochemistry analysis.

Results—
An irregular shape and large size was significantly related to UIA wall enhancement. Both uniform and focal wall enhancement may demonstrate the inflammation processes of UIA walls, although the latter may indicate more atherosclerotic plaque formation.

Conclusions—
Different high-resolution vessel wall magnetic resonance imaging enhancement features may represent variable inflammation status of a UIA wall, which may provide new insights into assessing the UIA wall structure and optimizing treatment.
Baseline Carotid Intima-Media Thickness and Stroke Recurrence During Secondary Prevention With Pravastatin
Authors: Wada Shinichi , Koga Masatoshi , Minematsu Kazuo , Toyoda Kazunori , Suzuki Rieko , Kagimura Tatsuo , Nagai Yoji , Aoki Shiro , Nezu Tomohisa , Hosomi Naohisa , Origasa Hideki , Ohtsuki Toshiho , Maruyama Hirofumi , Yasaka Masahiro , Kitagawa Kazuo , Uchiyama Shinichiro , Matsumoto Masayasu ,   on behalf of the Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study Collaborators
Published: April 2019

Background and Purpose—
As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated.

Methods—
Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT.

Results—

A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (<0.812 mm; [hazard ratio, 9.08; 95% CI, 1.15–71.43]). Patients in the pravastatin group had a lower risk of atherothrombotic brain infarction than those in the control group only in the highest tertile IMT group by the log-rank test (
P
value=0.045).

Conclusions—
Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00361530.
Incorporating User Values into Climate Services
Authors: Parker Wendy S. , Lusk Greg 
Published: April 2019

AbstractIncreasingly there are calls for climate services to be “co-produced” with users, taking into account not only the basic information needs of users but also their value systems and decision contexts. What does this mean in practice? One way that user values can be incorporated into climate services is in the management of inductive risk. This involves understanding which errors in climate service products would have particularly negative consequences from the users’ perspective (e.g., underestimating rather than overestimating the change in an impact variable) and then prioritizing the avoidance of those errors. This essay shows how inductive risk could be managed in climate services in ways that serve user values and argues that there are both ethical and practical reasons in favor of doing so.
Cytological-energy analysis of pleural effusions
Authors: Kelbich Petr , Malý Vilém , Matuchová Inka , Čegan Martin , Staněk Ivan , Král Jiří , Karpjuk Ondřej , Moudrá-Wünschová Irena , Kubalík Jan , Hanuljaková Eva , Krejsek Jan 
Published: April 2019

Background Simultaneous cytological and metabolic investigation of the pleural effusion provides clinically relevant information about the type and intensity of immune response in the pleural cavity. Methods We investigated 1329 pleural effusions from patients with different pathological changes in the pleural cavity. Evaluated parameters were differential cell count of neutrophils, eosinophils, lymphocytes and monocytes, and values of the coefficient of energy balance. Results We found the lowest numbers of cells and the highest coefficient of energy balance values in patients with heart failure and sepsis; relatively high frequency of eosinophils and slightly decreased coefficient of energy balance values in patients with pneumothorax and haemothorax; the predominance of lymphocytes and low coefficient of energy balance values in patients with tuberculous pleuritis; the predominance of neutrophils and variable coefficient of energy balance values in patients after chest surgery; the highest presence of neutrophils and very low coefficient of energy balance values in patients with chest empyema and the predominance of lymphocytes and normal to low coefficient of energy balance values in patients with pleural malignancy. Conclusions Our findings in patients with heart failure and sepsis suggest the absence of inflammation in the pleural cavity. We observed the manifestation of tissue repair in patients with pneumothorax and haemothorax. Patients with tuberculous pleuritis were predominantly characterized by T cell-driven immune response and oxidative burst of macrophages. We found different intensities of immune responses to the chest surgery. The typical finding in patients with empyema was oxidative burst of neutrophils. In patients with pleural malignancy, weak cytotoxic inflammation predominates together with the intensive inflammation characterized by oxidative burst of macrophages.
A liquid chromatography-tandem mass spectrometry assay for the profiling of classical and 11-oxygenated androgens in saliva
Authors: Schiffer Lina , Adaway Joanne E , Arlt Wiebke , Keevil Brian G 
Published: April 2019

Background Classical and 11-oxygenated androgens both contribute to the androgen pool. Regular monitoring of the androgen status is required in disorders of steroidogenesis, and multiplexing of androgens improves the diagnostic ability of an assay. Due to the cheap non-invasive collection, saliva is advantageous when multiple samples are required. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers sensitive, simultaneous quantification of steroids with short run times. Here, we have developed an LC-MS/MS assay for the simultaneous measurement of 17-hydroxyprogesterone, androstenedione, testosterone, 11β-hydroxyandrostenedione and 11-ketotestosterone in saliva. Methods Samples (300 μL unstimulated whole saliva) were prepared by supported liquid extraction with dichloromethane and were reconstituted in 40% methanol. After online solid phase extraction with C18 cartridges, liquid chromatography was performed on a C8 column using a water/methanol gradient containing 0.1% formic acid and 2 mmol/L ammonium acetate. A Waters TQ-S mass spectrometer was used for quantification. Results Total run time was 6.4 min. For all analytes, recovery was between 89% and 109%, ion suppression between 86% and 105%. Intra- and inter-assay comparisons showed a coefficient of variation <10% and the bias between measured and nominal concentration varied between –8% and 10%. Interference with a large set of natural and synthetic steroids was excluded. The assay was applied for the measurement of the androgen profile in healthy men ( n = 17) and women ( n = 10) which confirmed the sensitivity of the assay to be appropriate. Conclusion We present a novel LC-MS/MS assay for the comprehensive profiling of classical and 11-oxygenated androgens with potential for routine clinical application.
Characterization of galactosyl and lactosyl sulfatide species in human serum by MALDI-TOF mass spectrometry
Authors: Hori Atsushi , Yamaura Makoto , Morita Sunao , Uehara Takeshi , Honda Takayuki , Hidaka Hiroya 
Published: April 2019

Background Sulfatides are found in a variety of tissues and serum lipoproteins. Sulfatide is a molecular species composed of various sphingoid bases, fatty acids and sugar chains; therefore, rapid analysis of the qualitative structure is important in clinical assessment. Methods In this study, sulfatide-rich fractions were isolated from serum lipids, and the sulfatide species were analysed by negative ion mode using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results Sulfatide species identified in human serum included two different sugar chains, eight sphingoid molecules and various fatty acid side chains including hydroxy fatty acids. In total, 64 galactosyl sulfatides (SM4s) and 49 lactosyl sulfatides (SM3) were identified. Quantitatively, the amount of SM3 was less than 1% of the amount of SM4s. The fatty acids of SM4s of healthy serum ( n = 8) were predominantly C16:0 and a hydroxylation C16:0 (C16:0h), followed by very long chain fatty acids (VLCFAs) predominant species, and SM3 was a major component of VLCFAs. Conclusion This present study described a simple method of human serum sulfatide analysis using MALDI-TOF MS. This method is suitable for clinical laboratories and is likely to increase the understanding of the roles of sulfatide species in both physiological and disease states.
Externalizing and internalizing symptoms in childhood and adolescence and the risk of alcohol use disorders in young adulthood: A meta-analysis of longitudinal studies
Authors: Meque Ivete , Dachew Berihun Assefa , Maravilla Joemer C , Salom Caroline , Alati Rosa 
Published: April 2019

Background: Evidence suggests that externalizing and internalizing symptoms are expressed early in life and are associated with problematic drinking in young adulthood. However, few studies have examined their role during childhood and adolescence in predicting alcohol problems later in life. Objectives: To examine the role of childhood and adolescent externalizing and internalizing symptoms in predicting alcohol use disorders in young adulthood. Methods: We searched five electronic databases (PubMed, Scopus, PsycINFO, Web of Sciences and Embase) for studies which diagnosed alcohol use disorders through either the International Classification of Diseases or American Psychiatric Association – Diagnostic and Statistical Manual of Mental Disorders criteria and followed up children or adolescents into the transition to young adulthood. We performed a meta-analysis and obtained pooled odds ratio estimates with 95% confidence intervals using random-effects models. Results: A total of 12 longitudinal studies met eligibility criteria and were included in the meta-analysis. All measured the outcome using Diagnostic and Statistical Manual of Mental Disorders criteria. The majority were of good quality and were conducted in the United States. A total of 19,407 participants (50% female) were included in this meta-analysis. Of these, n = 2337 (12%) had diagnoses of alcohol use disorders/alcohol dependence. Participant ages ranged from birth to 36 years. Internalizing symptoms increased the risk of young adult alcohol use disorders by 21% (odds ratio = 1.21; 95% confidence interval = [1.05, 1.39]), with no strong evidence of publication bias. Subgroup analysis suggested significantly lower heterogeneity than for externalizing studies. Externalizing symptoms increased the risk of alcohol use disorders by 62% (odds ratio = 1.62, 95% confidence interval = [1.39, 1.90]). We found some evidence of publication bias and significant heterogeneity in the studies. Conclusion: Our findings highlight the contribution of early behavioural problems to the development of alcohol use disorders in young adulthood and the need for timely scrutiny of and intervention on early behavioural problems.
Beasts of Prey or Rational Animals? Private Governance in Brazil’s Jogo do Bicho
Authors: Freire Danilo 
Published: April 2019

A rational-choice account of Brazil’s jogo do bicho (animal game), possibly the largest illegal lottery game in the world, examines the mechanisms that have fostered the lottery’s notable growth outside the boundaries of Brazilian law and reveals how animal-game financiers combine costly signals and selective incentives to induce cooperation from members of the community and exploit the fragmentation of Brazil’s political system to advance their long-term interests. Uma abordagem da teoria da escolha racional do jogo do bicho, possivelmente o maior jogo de loteria ilegal do mundo, examina os mecanismos que fomentaram o crescimento notável da loteria fora dos limites da lei brasileira e revela como os financiadores de jogos de animais combinam caros sinais e incentivos seletivos para induzir a cooperação de membros da comunidade e explorar a fragmentação do sistema político brasileiro para promover seus interesses de longo prazo.
Factors Influencing Poor Outcomes in Synthetic Tissue‐Engineered Tracheal Replacement
Authors: Pepper Victoria , Best Cameron A. , Buckley Kaila , Schwartz Cynthia , Onwuka Ekene , King Nakesha , White Audrey , Dharmadhikari Sayali , Reynolds Susan D. , Johnson Jed , Grischkan Jonathan , Breuer Christopher K. , Chiang Tendy 
Published: April 2019

ObjectivesHumans receiving tissue‐engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside.Study DesignLarge animal model.SettingPediatric academic research institute.Subjects and MethodsHuman scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow–derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4‐month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry.ResultsAll animals had signs of graft stenosis. Three of 5 animals (60%) designated for long‐term surveillance survived until the 4‐month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination.ConclusionsIn our ovine model, clinically applied synthetic tissue‐engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.
Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems
Authors: Luethi Dino , Kolaczynska Karolina E , Walter Melanie , Suzuki Masaki , Rice Kenner C , Blough Bruce E , Hoener Marius C , Baumann Michael H , Liechti Matthias E 
Published: April 2019

Background: Amphetamine analogs with a 3,4-methylenedioxy ring-substitution are among the most popular illicit drugs of abuse, exerting stimulant and entactogenic effects. Enzymatic N-demethylation or opening of the 3,4-methylenedioxy ring via O-demethylenation gives rise to metabolites that may be pharmacologically active. Indeed, previous studies in rats show that specific metabolites of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV) can interact with monoaminergic systems. Aim: Interactions of metabolites of MDMA, methylone and MDPV with human monoaminergic systems were assessed. Methods: The ability of parent drugs and their metabolites to inhibit uptake of tritiated norepinephrine, dopamine and serotonin (5-HT) was assessed in human embryonic kidney 293 cells transfected with human monoamine transporters. Binding affinities and functional activity at monoamine transporters and various receptor subtypes were also determined. Results: MDMA and methylone displayed greater potency to inhibit norepinephrine uptake as compared to their effects on dopamine and 5-HT uptake. N-demethylation of MDMA failed to alter uptake inhibition profiles, whereas N-demethylation of methylone decreased overall transporter inhibition potencies. O-demethylenation of MDMA, methylone and MDPV resulted in catechol metabolites that maintained norepinephrine and dopamine uptake inhibition potencies, but markedly reduced activity at 5-HT uptake. O-methylation of the catechol metabolites significantly decreased norepinephrine uptake inhibition, resulting in metabolites lacking significant stimulant properties. Conclusions: Several metabolites of MDMA, methylone and MDPV interact with human transporters and receptors at pharmacologically relevant concentrations. In particular, N-demethylated metabolites of MDMA and methylone circulate in unconjugated form and could contribute to the in vivo activity of the parent compounds in human users.
Return to Play After the Latarjet Procedure for Anterior Shoulder Instability: A Systematic Review
Authors: Hurley Eoghan T. , Montgomery Connor , Jamal M. Shazil , Shimozono Yoshiharu , Ali Zakariya , Pauzenberger Leo , Mullett Hannan 
Published: April 2019

Background: Traumatic anterior shoulder instability is a common clinical problem among athletic populations. The Latarjet procedure is a widely used treatment option to address shoulder instability in high-demand athletes at high risk of recurrence. However, rates and timing of full return to sports have not been systematically analyzed. Purpose: To systematically review the evidence in the literature to ascertain the rate and timing of return to play and the availability of specific criteria for safe return to play after the Latarjet procedure. Study Design: Systematic review. Methods: A systematic literature search was conducted based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using the EMBASE, MEDLINE, and Cochrane Library databases. Eligible for inclusion were clinical studies reporting on return to play after the Latarjet procedure. Statistical analysis was performed by use of SPSS. Results: Our review found 36 studies including 2134 cases meeting our inclusion criteria. The majority of patients were male (86.9%), with a mean age of 25.4 years (range, 15-59 years) and a mean follow-up of 83.5 months. The overall rate of return to play was 88.8%, with 72.6% returning to the same level of play. Among collision athletes, the overall rate of return to play was 88.2%, with 69.5% returning to the same level of play. In overhead athletes, the overall rate of return to play was 90.3%, with 80.6% returning to the same level of play. The mean time to return to play was 5.8 months (range, 3.2-8 months). Specific return to play criteria were reported in the majority of the studies (69.4%); time to return to sport was the most commonly reported item (66.7%). Conclusion: The overall rate of return to play was reportedly high after the Latarjet procedure. However, almost a fifth of athletes returning to sports were not able to return at the same level. Further development of validated criteria for safe return to sports could potentially improve clinical outcomes and reduce recurrence rates.