Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas.
Widespread distribution of reticulon‐3 in various neurodegenerative diseases

Reticulons are a group of membrane‐bound proteins involved in diverse cellular functions, and are suggested to act as inhibitors of β‐secretase enzyme 1 (BACE1) activity that cleaves amyloid precursor protein. Reticulons are known to accumulate in the dystrophic neurites of Alzheimer's disease (AD), and studies have suggested that alterations in reticulons, such as increased aggregation, impair BACE1 binding, increasing amyloid‐β production, and facilitating reticulon deposition in dystrophic neurites. To further characterize the cellular distribution of reticulon, we examined reticulon‐3 expression in cases of AD, Parkinson's disease, and diffuse Lewy body disease. A more widespread cellular distribution of reticulon‐3 was noted than in previous reports, including deposits in dystrophic neurites, neuropil threads, granulovacuolar degeneration, glial cells, morphologically normal neurons in both hippocampal pyramidal cell layer and cerebral neocortex, and specifically neurofibrillary tangles and Lewy bodies. These results are compatible with reticulon alterations as nonspecific downstream stress responses, consistent with its expression during periods of endoplasmic reticulum stress. This emphasizes the increasing recognition that much of the AD pathological spectrum represents a response to the disease rather than cause, and emphasizes the importance of examining upstream processes, such as oxidative stress, that have functional effects prior to the onset of structural alterations.
Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial.

CONTEXT Effects of long-term calcium, with or without vitamin D, on hip bone mineral density (BMD) and bone turnover in sunny climates have not been reported. OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes. DESIGN, SETTING, AND PARTICIPANTS The study was a 5-yr randomized, controlled, double-blind trial of 120 community-dwelling women aged 70-80 yr. INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D (Ca group) or with 1000 IU/d vitamin D2 (CaD group), or double placebo (control). MAIN OUTCOME MEASURES Hip BMD, plasma 25-hydroxyvitamin D, biomarkers of bone turnover, PTH, and intestinal calcium absorption were measured. RESULTS Hip BMD was preserved in CaD (-0.17%) and Ca (0.19%) groups but not controls (-1.27%) at yr 1 and maintained in the CaD group only at yr 3 and 5. The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median (68 nmol/liter). At yr 1, compared with controls, the Ca and CaD groups had 6.8 and 11.3% lower plasma alkaline phosphatase, respectively (P<or=0.02), and 28.7 and 34.5% lower urinary deoxypyridinoline to creatinine ratio, respectively (P<or=0.05). At 5 yr, this suppression was maintained only in the CaD group. CaD reduced PTH at 3 and 5 yr cf. controls (27.8 and 31.3%, P<or=0.005) in those with baseline PTH levels above the median (3.6 pmol/liter). Therapy did not affect intestinal calcium absorption at high carrier loads. CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate, probably mediated by a long-term reduction in bone turnover rate.
Dual Hypocretin Receptor Antagonism Is More Effective for Sleep Promotion than Antagonism of Either Receptor Alone

The hypocretin (orexin) system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1) and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867) and HCRTR2 (EMPA) antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat. All 4 antagonists bound to their respective receptors with high affinity and selectivity in vitro. Since in vivo pharmacokinetic experiments revealed poor brain penetration for SB-408124, SB-334867 was selected for subsequent in vivo studies. When injected in the mid-active phase, SB-334867 produced small increases in rapid-eye-movement (REM) and non-REM (NR) sleep. EMPA produced a significant increase in NR only at the highest dose studied. In contrast, almorexant decreased NR latency and increased both NR and REM proportionally throughout the subsequent 6 h without rebound wakefulness. The increased NR was due to a greater number of NR bouts; NR bout duration was unchanged. At the highest dose tested (100 mg/kg), almorexant fragmented sleep architecture by increasing the number of waking and REM bouts. No evidence of cataplexy was observed. HCRTR1 occupancy by almorexant declined 4–6 h post-administration while HCRTR2 occupancy was still elevated after 12 h, revealing a complex relationship between occupancy of HCRT receptors and sleep promotion. We conclude that dual HCRTR1/R2 blockade is more effective in promoting sleep than blockade of either HCRTR alone. In contrast to GABA receptor agonists which induce sleep by generalized inhibition, HCRTR antagonists seem to facilitate sleep by reducing waking “drive”.
Perceptions and Expectations of Roles and Responsibilities of Literacy Coaching

Having specialists in schools providing guidance for classroom teachers and addressing students' literacy issues is widely accepted. The roles these educators fulfill have changed over the years and the expectations of the role differ among professionals providing and receiving services. The purpose of this study was to explore the perceptions of principals, teachers, and school-based literacy specialists on how literacy coaching can be effectively used and to consider the implications of these perceptions and expectations in terms of the potential for coaching to contribute to the development and implementation of effective literacy programs. We found few differences in responses among the professionals we surveyed; however, outcomes from interviews presented a somewhat different picture. Responses to interview questions indicate that the role of the literacy coach is currently open to much interpretation on the part of principals, teachers, and the coaches themselves. Participants consistently expressed the desire to establish and clearly communicate the literacy coach's schedule of activities, and to offer opportunities for coaches to apply and enhance their specialized training.
Measurement Invariance in Careers Research

The current study demonstrates the use of item response theory (IRT) to conduct measurement invariance analyses in careers research. A self-report survey was used to assess the importance 1,363 fourth-year medical students placed on opportunities to provide comprehensive patient care when choosing a career specialty. IRT analyses supported measurement invariance across gender. Additional analyses indicated that compared with men, women placed significantly greater importance on opportunities to provide comprehensive patient care. This in turn predicted career choice, with women being more likely than men to pursue primary care specialties. This study extends the careers literature both methodologically and substantively. Methodologically, this study exemplifies how and why to use IRT to assess measurement invariance prior to comparing groups on career-related attitudes. Substantively, this study is the first to demonstrate that the importance placed on comprehensive patient care mediates the effect of gender on intentions to pursue primary care specialties.
Toll-like receptor expression in monocytes in patients with chronic kidney disease and haemodialysis: relation with inflammation.

BACKGROUND Inflammation is one of the main contributors to atherosclerosis in haemodialysis (HD) patients. Activation of Toll-like receptors (TLRs) leads to inflammatory response. In this study, we aimed to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in chronic kidney disease (CKD) and HD patients. METHODS Thirty-four age- and gender-matched controls and stage 3-4 CKD patients and thirty-two HD patients were included in each study group. The effect of HD on the expression of Toll-like receptor-2 (TLR-2) and Toll-like receptor-4 (TLR-4) on CD14( +) monocytes was determined at the beginning (baseline), during (120 min) and following (300 min and 24 h) HD and compared with control and stage 3-4 CKD groups. The HD procedure was performed by using low-flux polysulphone dialysers. In addition, serum IL-6 levels were evaluated in both groups at baseline and after a HD session. RESULTS The percentage of CD14( +) monocytes expressing TLR-2 were similar in all of the study groups, whereas the percentage of CD14( +) monocytes expressing TLR-4 were significantly lower in both stage 3-4 CKD and HD patients at baseline than in controls. The mean fluorescence intensities (MFI) of TLR-2 were significantly lower in controls than in stage 3-4 CKD and HD patients at baseline. The MFI of TLR-4 was similar in all of the groups. The percentage of CD14( +) monocytes expressing TLR-2 did not change during and after HD. The MFI of TLR-2 decreased at 120 min of HD compared with baseline (1837 ± 672 vs 1650 ± 578, P < 0.05), and recovered back to baseline values at 300 min and at 24 h post-HD. MFI of TLR-4 increased at 24 h compared with baseline (941 ± 294 vs 1087 ± 441, P < 0.05). Serum IL-6 levels correlated with MFI of TLR-2 and TLR-4 in stage 3-4 CKD patients and in HD patients at baseline and after HD in univariate analysis. Stepwise multiple regression analysis revealed that MFI of TLR-2 was an independent determinant of serum IL-6 concentrations in stage 3-4 CKD and in HD patients at baseline, at 300 min and at 24 h post-HD. Conclusions. Our study demonstrates that TLR-2 is associated with the inflammatory response of non-dialysed and dialysed CKD patients.
Nature of Priming Effects on Categorization

Alternative models for explaining priming effects on categorization are described, and their predictions concerning the relative advantage of frequent versus recent priming as a function of interstimulus delay are contrasted. Subjects were asked to categorize an ambiguous stimulus description that could be characterized in either a positive or a negative manner. Prior to its presentation, subjects were unobtrusively exposed to both positive and negative primes related to the description. For half of the subjects, the positive primes appeared more frequently, but the negative prime appeared most recently; for the remaining subjects, the negative primes appeared more frequently, but the positive prime appeared most recently. Between the final prime and stimulus presentation, there was a delay of either 15 s or 120 s, Subjects tended to categorize the stimulus description in terms of the recently primed construct after the brief interstimulus delay, but they tended to categorize the description in terms of the frequently primed construct after the long interstimulus delay. These results are consistent with a proposed synapse model of priming effects. Other possible models that make different assumptions about the level of activation, the decay function, and their ability to account for the findings are discussed.
Ageism and Death: Effects of Mortality Salience and Perceived Similarity to Elders on Reactions to Elderly People

The present research investigated the hypotheses that elderly people can be reminders of our mortality and that concerns about our own mortality can therefore instigate ageism. In Study 1, college-age participants who saw photos of two elderly people subsequently showed more death accessibility than participants who saw photos of only younger people. In Study 2, making mortality salient for participants increased distancing from the average elderly person and decreased perceptions that the average elderly person possesses favorable attitudes. Mortality salience did not affect ratings of teenagers. In Study 3, these mortality salience effects were moderated by prior reported similarity to elderly people. Distancing from, and derogation of, elderly people after mortality salience occurred only in participants who, weeks before the study, rated their personalities as relatively similar to the average elderly person’s. Discussion addresses distinguishing ageism from other forms of prejudice, as well as possibilities for reducing ageism.
Development as an Explanation for and Predictor of Online Self-Disclosure Among Dutch Adolescents

The goal of the present study was to investigate whether adolescent online self-disclosure is primarily related to the developmental variable of egocentrism or related to the personality trait, narcissism. Egocentrism was measured as Imaginary Audience ideation and Personal Fable ideation, two distinct concepts of adolescent egocentrism. We also examined whether age moderates the aforementioned relationship. A total of 381 participants completed the survey instrument. The sample consisted of adolescents from two high schools and college students in the Netherlands. Results indicated a positive relationship between Imaginary Audience ideation and Facebook self-disclosure. Also, more narcissistic adolescents disclosed more on Facebook than less narcissistic adolescents. However, this effect became weaker when controlling for Imaginary Audience ideation. Finally, Imaginary Audience was related to Facebook self-disclosure for all age groups except the 19–22 age group. Thus, adolescent egocentrism is a somewhat stronger a predictor of online self-disclosure than narcissism.
Models of Concentration in Natural Environments: A Comparative Approach Based on Streams of Experiential Data

In this paper we investigated a prediction from flow theory according to which subjective feelings of concentration depend on the balance between perceived challenges posed by a task and one’s perceived skills in mastering the task. The goal was to compare 3 different formalizations of balance (crossproduct, absolute difference, and quadratic effects of challenges and skills following a rotation of the predictor axes) with respect to how well each model predicts everyday life self-reports of feelings of con-centration, which were obtained with the experience sampling method from 208 talented high school students. Multilevel modeling with first-order autocorrelation structure was used throughout the model comparison. All models fitted reasonably well, accounting for nearly half of the variance. With reference to simple goodness-of-fit criteria, we concluded that both the rotated and the absolute difference models are to be preferred. Lastly, we discussed and compared the implications of the models for teaching, and outlined extensions toward dynamic modeling and external modeling, by relating the subject-specific effects of challenges and skills and of their balance with non-experiential variables such as personality traits and achievement measures.
Monitoring respiratory and cardiac motion in CT using a continuous wave Doppler radar

Poster: "ECR 2013 / C-2055 / Monitoring respiratory and cardiac motion in CT using a continuous wave Doppler radar" by: "F. Pfanner1, T. Allmendinger2, T. Flohr2, M. Kachelries3; 1Erlangen/DE, 2Forchheim/DE, 3Heidelberg/DE"
Effects of a Carbohydrate-, Protein-, and Ribose-Containing Repletion Drink During 8 Weeks of Endurance Training on Aerobic Capacity, Endurance Performance, and Body Composition

Abstract Cramer, JT, Housh, TJ, Johnson, GO, Coburn, JW, and Stout, JR. Effects of a carbohydrate-, protein-, and ribose-containing repletion drink during 8 weeks of endurance training on aerobic capacity, endurance performance, and body composition. J Strength Cond Res 26(8): 2234–2242, 2012—This study compared a carbohydrate-, protein-, and ribose-containing repletion drink vs. carbohydrates alone during 8 weeks of aerobic training. Thirty-two men (age, mean ± SD = 23 ± 3 years) performed tests for aerobic capacity (V[Combining Dot Above]O2peak), time to exhaustion (TTE) at 90% V[Combining Dot Above]O2peak, and percent body fat (%fat), and fat-free mass (FFM). Testing was conducted at pre-training (PRE), mid-training at 3 weeks (MID3), mid-training at 6 weeks (MID6), and post-training (POST). Cycle ergometry training was performed at 70% V[Combining Dot Above]O2peak for 1 hours per day, 5 days per week for 8 weeks. Participants were assigned to a test drink (TEST; 370 kcal, 76 g carbohydrate, 14 g protein, 2.2 g d-ribose; n = 15) or control drink (CON; 370 kcal, 93 g carbohydrate; n = 17) ingested immediately after training. Body weight (BW; 1.8% decrease CON; 1.3% decrease TEST from PRE to POST), %fat (5.5% decrease CON; 3.9% decrease TEST), and FFM (0.1% decrease CON; 0.6% decrease TEST) decreased (p ⩽ 0.05), whereas V[Combining Dot Above]O2peak (19.1% increase CON; 15.8% increase TEST) and TTE (239.1% increase CON; 377.3% increase TEST) increased (p ⩽ 0.05) throughout the 8 weeks of training. Percent decreases in %fat from PRE to MID3 and percent increases in FFM from PRE to MID3 and MID6 were greater (p ⩽ 0.05) for TEST than CON. Overall, even though the TEST drink did not augment BW, V[Combining Dot Above]O2peak, or TTE beyond carbohydrates alone, it did improve body composition (%fat and FFM) within the first 3–6 weeks of supplementation, which may be helpful for practitioners to understand how carbohydrate-protein recovery drinks can and cannot improve performance in their athletes.
Electrospinning of polyhydroxyalkanoate fibrous scaffolds: effects on electrospinning parameters on structure and properties

In this study, electrospinning was used to prepare ultrafine fibers from PHAs with different chemical compositions: P(3HB) and copolymers: P(3HB-co-4HB), P(3HB-co-3HV), and P(3HB-co-3HHx). The main process parameters that influence ultrafine fiber diameter and properties (polymer concentration, solution feeding rate, working distance, and applied voltage) have been investigated and their effects evaluated. The study revealed electrospinning parameters for the production of high-quality ultrafine fibers and determined which parameters should be varied to tailor the properties of the products. This study is the first to compare biological and physical-mechanical parameters of PHAs with different chemical compositions as dependent upon the fractions of monomers constituting the polymers and ultrafine fiber orientation. Mechanical strength of aligned ultrafine fibers prepared from different PHAs is higher than that of randomly oriented ones; no significant effect of ultrafine fiber orientation on surface properties has been found. None of the fibrous scaffolds produced by electrospinning from PHAs had any adverse effects on attachment, growth, and viability of NIH 3T3 mouse fibroblast cells, and all of them were found to be suitable for tissue engineering applications.
Model for a novel membrane envelope in a filamentous hyperthermophilic virus

Biological membranes create compartments, and are usually formed by lipid bilayers. However, in hyperthermophilic archaea that live optimally at temperatures above 80°C the membranes are monolayers which resemble fused bilayers. Many double-stranded DNA viruses which parasitize such hosts, including the filamentous virus AFV1 of Acidianus hospitalis, are enveloped with a lipid-containing membrane. Using cryo-EM, we show that the membrane in AFV1 is a ~2 nm-thick monolayer, approximately half the expected membrane thickness, formed by host membrane-derived lipids which adopt a U-shaped ‘horseshoe’ conformation. We hypothesize that this unusual viral envelope structure results from the extreme curvature of the viral capsid, as ‘horseshoe’ lipid conformations favor such curvature and host membrane lipids that permit horseshoe conformations are selectively recruited into the viral envelope. The unusual envelope found in AFV1 also has many implications for biotechnology, since this membrane can survive the most aggressive conditions involving extremes of temperature and pH. DOI: http://dx.doi. org/10.7554/eLife.26268. 001
Cross-cultural differences in the perception of female body shapes

Synopsis Whereas in Western societies there is an inverse relationship between high social class and low body weight, the inverse is true of less developed, non-Western societies. It has also been shown that the longer immigrants have been in Western societies, the less obese they tend to be. This study examined how Kenyan Asian, British and Kenyan British females from similar backgrounds perceived female body shapes. As predicted, the Kenyans rated larger figures more favourably and smaller figures less favourably than the British. Also, as predicted, it was found that the Kenyan Asian British were more similar to the British group in their perceptions. The results support the view that social and cultural factors play dominant role in the perception of one's own and others' body shapes. In addition, the results reveal that in Britain preferences for small body shapes to the point of being anorexic are not uncommon.