bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization and quantification of mitochondrial structure in the endothelium of intact arteries
Authors: Durand Matthew J , Ait-Aissa Karima , Levchenko Vladislav , Staruschenko Alexander , Gutterman David D , Beyer Andreas M 
Published: November 2018

Abstract

Aim
To quantify the mitochondrial structure of ECs in intact arteries vs. cultured cells.

Methods and results
Cre-stop mito-Dendra2 mice, expressing the fluorescent protein Dendra2 in the mitochondrial matrix only, were used to label EC mitochondria using Cre-recombinase under the control of the VE-cadherin promoter. Conduit arteries, resistance arterioles and veins were fixed, mounted on glass slides and fluorescent images were obtained using a laser scanning confocal microscope (ex 488 nm; em 550 nm). ImageJ was used to calculate form factor (FF) and aspect ratio (AR) of the mitochondrial segments. Mitochondrial fragmentation count (MFC) was calculated by counting non-contiguous mitochondrial particles and dividing by the number of pixels which comprise the mitochondrial network. Primary aortic EC cultures (48 h on culture plates) were generated to compare the mitochondrial structure of cultured ECs vs. intact arteries. Aortic segments were also exposed to high glucose overnight (33 mM) ex vivo, and separate groups of mice were either infused with a high-glucose saline solution (300 mM) via tail vein catheter for 1 h or injected with streptozotocin (STZ; 50 mg/kg) to cause hyperglycaemia. Compared with cultured ECs, the mitochondria of ECs from the intact aorta were more fragmented (MFC: 6.4 ± 2.5 vs. 18.6 ± 9.4, respectively; P < 0.05). The mitochondrial segments of ECs within the aorta were more circular in shape (FF: 3.5 ± 0.75 vs. 1.8 ± 0.30, respectively; P < 0.05) and had less branching (AR: 2.9 ± 0.60 vs. 2.0 ± 0.25, respectively; P < 0.05) compared with cultured ECs. Ex vivo exposure of the intact aorta to high glucose overnight caused mitochondrial fission compared with normal glucose conditions (5 mM; MFC: 25.5 ± 11.1 high glucose vs. 11.0 ± 3.6 normal glucose; P < 0.05). Both 1-h infusion of high glucose saline (MFC: 22.4 ± 4.3) and STZ treatment (MFC: 40.3 ± 14.2) caused mitochondrial fission compared with freshly fixed aortas from control mice (MFC: 18.6 ± 9.4; P < 0.05 vs. high-glucose infusion and STZ treatment).

Conclusions
Using a novel mouse model, we were able to, for the first time, obtain high resolution images of EC mitochondrial structure in intact arteries. We reveal the endothelial mitochondrial network is more fragmented in the intact aorta compared with cultured ECs, indicating that mitochondria assume a more elongated and branched phenotype in cell culture.
RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production
Authors: Sasanuma Hiroki , Ozawa Manabu , Yoshida Nobuaki 
Published: November 2018

Abstract
The RNA-binding protein polypyrimidine tract-binding protein-1 (Ptbp1) binds to the pyrimidine-rich sequence of target RNA and controls gene expression via post-transcriptional regulation such as alternative splicing. Although Ptbp1 is highly expressed in B lymphocytes, its role to date is largely unknown. To clarify the role of Ptbp1 in B-cell development and function, we generated B-cell-specific Ptbp1-deficient (P1BKO) mice. B-cell development in the bone marrow, spleen and peritoneal cavity of the P1BKO mice was nearly normal. However, the P1BKO mice had significantly lower levels of natural antibodies in serum compared with those of the control mice. To investigate the effect of Ptbp1 deficiency on the immune response in vivo, we immunized the P1BKO mice with T-cell-independent type-2 (TI-2) antigen NP-Ficoll and T-cell-dependent (TD) antigen NP-CGG. We found that B-cell-specific Ptbp1 deficiency causes an immunodeficiency phenotype due to defective production of antibody against both TI-2 and TD antigen. This immunodeficiency was accompanied by impaired B-cell receptor (BCR)-mediated B-cell activation and plasmablast generation. These findings demonstrate that Ptbp1 is essential for the humoral immune response.
Between spilling over and boiling down: network-mediated spillovers, local knowledge base and productivity in European regions
Authors: Cortinovis Nicola , van Oort Frank 
Published: November 2018

AbstractProductivity across European regions is related to three types of networks that mediate R&D-related knowledge spillovers: trade, co-patenting and geographical proximity. Both our panel and instrumental variable estimations for European regions suggest that network relations are crucial sources of R&D spillovers, but with potentially different features. Both import and co-patenting relations affect local productivity directly, but spillovers from innovation-leading regions are effective only when they are import-mediated and when recipient regions have a solid knowledge base. From a policy perspective, this may frustrate recent European policy initiatives, such as Smart Specialization, which are designed to benefit all regions in Europe.
Cirrus: An Automated Mammography-Based Measure of Breast Cancer Risk Based on Textural Features
Authors: Schmidt Daniel F , Makalic Enes , Goudey Benjamin , Dite Gillian S , Stone Jennifer , Nguyen Tuong L , Dowty James G , Baglietto Laura , Southey Melissa C , Maskarinec Gertraud , Giles Graham G , Hopper John L 
Published: November 2018

AbstractBackgroundWe applied machine learning to find a novel breast cancer predictor based on information in a mammogram.MethodsUsing image-processing techniques, we automatically processed 46 158 analog mammograms for 1345 cases and 4235 controls from a cohort and case–control study of Australian women, and a cohort study of Japanese American women, extracting 20 textural features not based on pixel brightness threshold. We used Bayesian lasso regression to create individual- and mammogram-specific measures of breast cancer risk, Cirrus. We trained and tested measures across studies. We fitted Cirrus with conventional mammographic density measures using logistic regression, and computed odds ratios (OR) per standard deviation adjusted for age and body mass index.ResultsCombining studies, almost all textural features were associated with case–control status. The ORs for Cirrus measures trained on one study and tested on another study ranged from 1.56 to 1.78 (all P < 10−6). For the Cirrus measure derived from combining studies, the OR was 1.90 (95% confidence interval [CI] = 1.73 to 2.09), equivalent to a fourfold interquartile risk ratio, and was little attenuated after adjusting for conventional measures. In contrast, the OR for the conventional measure was 1.34 (95% CI = 1.25 to 1.43), and after adjusting for Cirrus it became 1.16 (95% CI = 1.08 to 1.24; P = 4 × 10−5).ConclusionsA fully automated personal risk measure created from combining textural image features performs better at predicting breast cancer risk than conventional mammographic density risk measures, capturing half the risk-predicting ability of the latter measures. In terms of differentiating affected and unaffected women on a population basis, Cirrus could be one of the strongest known risk factors for breast cancer.
“Hard Times Make for Hard Arteries and Hard Livers”: Deindustrialization, Biopolitics, and the Making of a New Working Class
Authors: Winant Gabriel 
Published: November 2018

Abstract
This article argues for a view of “actually existing neoliberalism,” identifying points of continuity from midcentury social democracy and showing how American neoliberalism developed unevenly across a preexisting landscape. It does so with a case study of labor market transformation in Pittsburgh, showing a causal relationship between the New Deal state’s institutional structures and the rise of low-wage employment in health care in the 1970s and 1980s. The low-wage service economy did not only come after the high-wage industrial economy: it grew out of it, sped by the decline of steel manufacturing and shaped within the distinctive matrix of the postwar public-private welfare. In establishing this historical process, the article also suggests that social history can play a useful conceptual role linking Foucauldian and Marxist accounts of neoliberalism, by showing concretely the role of the production of subjectivity and the governance of population in the establishment of the neoliberal economic regime. Pointing to a homology between the structural role of incarceration in neoliberalism and that of health care, the article suggests the term “biopolitical Keynesianism” for understanding this conceptual synthesis, which uncovers new contradictions within neoliberalism.
Impact of the Society for Research on Nicotine and Tobacco Health Disparities Network’s Scholarship on Professional Development of Its Recipients
Authors: Davis Danielle R , Hickman Norval J , Choi Kelvin , Robinson Cendrine D , Patten Christi A , Fagan Pebbles , Okuyemi Kolawole S , Nahvi Shadi 
Published: November 2018

Abstract

Introduction
Diversifying the workforce is an important strategy to reducing health disparities. Since 2007, the Society for Research on Nicotine and Tobacco (SRNT) Health Disparities Network has funded a travel scholarship to promote inclusion, professional development, and diversity among investigators interested in tobacco-related health disparities research. This study examined indicators of productivity among former scholarship recipients.
Methods: Scholarship recipients between 2007 and 2014 were invited to complete a survey online. The survey assessed demographic characteristics, academic productivity, and perceived professional benefit resulting from the scholarship.
Results: Of the 117 scholarships recipients, 89 (77%) responded. Respondents were 67% female and had a mean age of 37.8 years. Twenty eight percent were African American, 25% Asian American, and 17% Latino. Most respondents worked in academia (80%) and nearly three-quarters (74%) reported publishing manuscripts on tobacco-related disparities, with a mean of 3.8 (SD 4.4) disparities-related publications since receiving the scholarship. Respondents’ work focused on a wide range of health disparities topics and nearly all respondents reported that the scholarship removed barriers to attending the meeting and reported professional benefit from receiving the travel scholarship. Following receipt of the SRNT travel scholarship, a diverse group of scientists demonstrated scholarly productivity, professional development, and advancement of health disparities research. Similar efforts are encouraged in other professional societies.

Implications
This study examines the productivity of early career recipients of the SRNT Health Disparities Scholarship. Results suggest that the investment in annual travel scholarships by a professional organization is an important support system for emerging scientists from diverse backgrounds. This investment may help to advance the science of health disparities and engage researchers in an area where there are critical gaps in the research workforce.
Sex disparities in clinical characteristics and prognosis of immunoglobulin G4–related disease: a prospective study of 403 patients
Authors: Wang Liwen , Zhang Panpan , Zhang Xia , Lin Wei , Tang Hanqi , Li Jieqiong , Wang Mu , Liu Xiaowei , Fei Yunyun , Chen Hua , Peng Linyi , Zhang Li , Lai Yamin , Zeng Xuejun , Li Xuemei , Xue Huadan , Zhao Yan , Zhang Fengchun , Zhang Wen 
Published: November 2018

Abstract

Objectives
To study the impact of sex on the clinical presentation of IgG4-related disease (IgG4-RD).

Methods
We prospectively enrolled 403 newly diagnosed IgG4-RD patients. We compared the demographic features, clinical manifestations, organ involvement, laboratory tests and treatment outcomes between female and male patients. The organs involved were divided into superficial organs (salivary glands, lacrimal glands, orbit, sinus and skin) and internal organs (all the other organs). The patients treated with glucocorticoids with or without additional immunosuppressants were included in the assessment of treatment outcomes, and potential confounding factors were corrected by propensity score matching or multivariate Cox regression analysis.

Results
Female patients showed younger age at both symptom onset and diagnosis, and a longer interval between symptom onset and diagnosis. Allergy history, Mikulicz’s disease and thyroiditis were more common in female patients, while autoimmune pancreatitis, sclerosing cholangitis and retroperitoneal fibrosis were more common in male patients. In accordance, female patients more frequently presented with superficial organ involvement, while male patients more frequently had internal organ involvement, and the discrepancy was more prominent in the patients with older age. Male sex was associated with higher peripheral eosinophils, CRP and IgG4 levels at baseline. In response to glucocorticoid-based therapies, male sex was associated with a higher IgG4-RD responder index during follow-up as well as a greater risk of relapse (hazard ratio 3.14, P = 0.003).

Conclusion
Our study revealed the sex disparities in clinical characteristics of IgG4-RD, and indicated that male sex was independently associated with worse prognosis in response to glucocorticoid-based therapies.
DETRIMENTS IN NEURON MORPHOLOGY FOLLOWING HEAVY ION IRRADIATION: WHAT’S THE TARGET?
Authors: Cucinotta Francis A , Eliedonna Cacao Murat Alp 
Published: November 2018

Abstract
Neuron cells consist of the soma or cell body, axons, dendritic arbor with multiple branches, and dendritic spines which are the substrates for memory storage and synaptic transmission. Detriments in neuron morphology are suggested to play a key role in cognitive impairments following brain irradiation. Multiple molecular mechanisms are involved in the regulation and stability of neuron morphology, while the effects of radiation on these processes have not been studied extensively. In this report, we consider possible biological targets in neurons for energy deposition (ED) by charged particles that could lead to neuron morphology detriments, and the resulting dose and radiation quality dependence of such detriments. The track structures of heavy ions including high charge and energy (HZE) particles consists of core of high-ED events and a penumbra of sparse ED from δ-ray electrons produced in ionization of target molecules. We consider the role of track structure relative to possible targets causative in the degradation of morphology.
Adolescent Paranoia: Prevalence, Structure, and Causal Mechanisms
Authors: Bird Jessica C , Evans Robin , Waite Felicity , Loe Bao S , Freeman Daniel 
Published: November 2018

AbstractBackgroundAdolescence can be a challenging time, characterized by self-consciousness, heightened regard for peer acceptance, and fear of rejection. Interpersonal concerns are amplified by unpredictable social interactions, both online and offline. This developmental and social context is potentially conducive to the emergence of paranoia. However, research on paranoia during adolescence is scarce.MethodOur aim was to examine the prevalence, structure, and probabilistic causal mechanisms of adolescent paranoia. A representative school cohort of 801 adolescents (11–15 y) completed measures of paranoia and a range of affective, cognitive, and social factors. A Bayesian approach with Directed Acyclic Graphs (DAGs) was used to assess the causal interactions with paranoia.ResultsParanoid thoughts were very common, followed a continuous distribution, and were hierarchically structured. There was an overall paranoia factor, with sub-factors of social fears, physical threat fears, and conspiracy concerns. With all other variables controlled, DAG analysis identified paranoia had dependent relationships with negative affect, peer difficulties, bullying, and cognitive-affective responses to social media. The causal directions could not be fully determined, but it was more likely that negative affect contributed to paranoia and paranoia impacted peer relationships. Problematic social media use did not causally influence paranoia.ConclusionsThere is a continuum of paranoia in adolescence and occasional suspicions are common at this age. Anxiety and depression are closely connected with paranoia and may causally contribute to its development. Paranoia may negatively impact adolescent peer relationships. The clinical significance of paranoia in adolescents accessing mental health services must now be established.
Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes
Authors: Mobasheri Ali , van Spil Willem Evert , Budd Emma , Uzieliene Ilona , Bernotiene Eiva , Bay-Jensen Anne-Christine , Larkin Jonathan , Levesque Marc C. , Gualillo Oreste , Henrotin Yves 
Published: November 2018

Purpose of review
This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these correspond to clinical phenotypes.

Recent findings
Emerging evidence suggests that osteoarthritis is a heterogeneous and multifaceted disease with multiple causes, molecular endotypes and corresponding clinical phenotypes. Biomarkers may be employed as tools for patient stratification in clinical trials, enhanced disease management in the primary care centres of the future and for directing more rational and targeted osteoarthritis drug development. Proximal molecular biomarkers (e.g synovial fluid) are more likely to distinguish between molecular endotypes because there is less interference from systemic sources of biomarker noise, including comorbidities.

Summary
In this review, we have focused on the molecular biomarkers of four distinct osteoarthritis subtypes including inflammatory, subchondral bone remodelling, metabolic syndrome and senescent age-related endotypes, which have corresponding phenotypes. Progress in the field of osteoarthritis endotype and phenotype research requires a better understanding of molecular biomarkers that may be used in conjunction with imaging, pain and functional assessments for the design of more effective, stratified and individualized osteoarthritis treatments.
Urinary N-Telopeptide Can Predict Pseudarthrosis After Anterior Cervical Decompression and Fusion
Authors: Steinhaus Michael E. , Hill Patrick S. , Yang Jingyan , Feuchtbaum Eric , Bronheim Rachel S. , Prabhakar Pooja , Lafage Virginie , Carlson Brandon B. , Saville Philip , Albert Todd J. , Lafage Renaud , Stein Emily M. , Kim Han J. 
Published: November 2018

Study Design.
Prospective cohort study.

Objective.
To examine preoperative urinary cross-linked n-telopeptide (uNTx) and assess for association with fusion rates in patients undergoing single and multi-level anterior cervical decompression and fusion (ACDF).

Summary of Background Data.
Although high rates of fusion have been reported for ACDF, the risk of pseudarthrosis remains substantial. An established marker of bone turnover, uNTx may prove useful as a predictor of fusion.

Methods.
Patients undergoing primary ACDF with allograft/plating technique from 2015 to 2017 by a single surgeon were consecutively enrolled and preoperative uNTx was collected. Patients undergoing revision, with creatinine >1.2, and with improperly-collected uNTx were excluded. Demographics, laboratory values, and fusion status were assessed at 6 months, 1 year, and 2 years postoperatively.

Results.
Of the 97 patients enrolled, 69 met inclusion criteria. Of included cases, 41%, 33%, 18%, and 8% underwent 1-, 2-, 3-, and 4-level ACDF, respectively. Overall, fusion rates were 37.3%, 70.9%, and 95.3% at 6 months, 1 year, and 2 years, respectively. uNTx was higher in the fusion group (31.1 vs. 22.2, P = 0.001) at 6 months and 1 year (30.0 vs. 21.0, P = 0.006), with no difference at 2 years. No differences were identified in the proportion of smokers, immunomodulatory agents, corpectomies, or fusion levels between groups. Multivariate regression analysis demonstrated that uNTx is an independent predictor of fusion (odds ratio, OR, 1.124, P = 0.003). Both groups experienced improvements in NDI and VAS neck pain at 6 months with no significant differences noted between groups. Of 16 patients with pseudarthrosis at 1 year, 2 underwent posterior cervical fusion for symptoms.

Conclusion.
Preoperative uNTx was greater in patients with successful ACDF fusion compared with patients with pseudarthrosis at 6 months and 1 year. A negative correlation was found between preoperative uNTx and motion on dynamic imaging. These results suggest that uNTx could serve to identify patients at risk for pseudarthrosis after ACDF.

Level of Evidence: 3
Does Decreased Surgical Stress Really Improve the Psychosocial Health of Early-onset Scoliosis Patients?
Authors: Aslan Cihan , Olgun Z. Deniz , Ayik Gokhan , Karaokur Remzi , Ozusta Seniz , Demirkiran Gokhan Halil , Unal Fatih , Yazici Muharrem 
Published: November 2018

Study Design.
Cross-sectional case-control study.

Objective.
Compare psychosocial profile of magnetically-controlled growing rod (MCGR) patients to traditional-growing rod (TGR) with an array of psychiatric tools, expecting improvement in MCGR due to decreased number of surgical procedures.

Summary of Background Data.
TGR treatment has had positive clinical and radiographic results; however, upward of 10 surgical sessions and high complication rates have called into question the quality of life of these children. Improvement with the introduction of the MCGR is expected.

Methods.
GR patients with minimum of 2-years follow-up were recruited. None had neurological conditions. All underwent testing with the Wechsler Intelligence Scale for Children-Revised, and only those in the normal range were included. Patients filled out questionnaires with mental health professionals to measure psychosocial status. MCGR patients’ results were compared to TGR patients.

Results.
Twenty-seven patients met criteria (10 MCGR, 17 TGR): average age at enrollment 11.8 years (range 5.9–17). MCGR group was significantly younger (9.1 vs. 13.3 yr) and had significantly shorter follow-up (45.6 vs. 82.8 mo) (P < 0.05). TGR patients underwent an average of 16 surgical procedures, MCGR an average of 1.5 (including complications, P < 0.05). Age at index surgery (6 yr), preoperative and postoperative major curve magnitudes (60°, 40° respectively) were statistically similar.
There was no difference in current psychiatric diagnoses between the groups. MCGR patients scored worse than TGR patients in general functionality domains. TGR patients showed increased functionality and prosocial scores with increased number of procedures. This effect was not observed in MCGR.

Conclusions.
The expected improvement in psychosocial status with the MCGR was not observed at a 31.6-month-follow-up. It appears that provided the patient spends enough time in the treatment process to notice benefit and does not experience major complications, noninvasiveness of lengthening procedures does not show up as an advantage with the psychosocial tools utilized in this study.

Level of Evidence: 3