Miracle-dz/UniFAR-FTUs huggingface dataset:
Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect.
Modulation of Rho Guanine Exchange Factor Lfc Activity by Protein Kinase A-Mediated Phosphorylation

ABSTRACT Lfc is a guanine nucleotide exchange factor (GEF) for Rho that demonstrates an unusual ability to associate with microtubules. While several phosphorylated residues have been detected in the Lfc polypeptide, the mechanism(s) by which phosphorylation regulates the exchange activity of Lfc remains unclear. We confirm that Lfc is a phosphorylated protein and demonstrate that 14-3-3 interacts directly and in a phosphorylation-dependent manner with Lfc. We identify AKAP121 as an Lfc-binding protein and show that Lfc is phosphorylated in an AKAP-dependent manner by protein kinase A (PKA). Forskolin treatment induced 14-3-3 binding to Lfc and suppressed the exchange activity of wild-type Lfc on RhoA. Importantly, a mutant of Lfc that is unable to associate with 14-3-3 proteins was resistant to inhibition by forskolin. Tctex-1, a dynein motor light chain, binds to Lfc in a competitive manner with 14-3-3.
Nuclear Fuel Plate Fabrication Employing Friction Welding

This paper provides an overview of the friction bonding process, a novel modification of the more conventional friction stir welding process. The process has been modified to enable the fabrication of plate-type nuclear fuels for the conversion of research and test reactors currently operating using highly enriched uranium to low-enriched uranium. Discussions related to the specific modifications of the friction bonding process have been provided, in addition to challenges associated with these modifications. Progression of the process and solutions to the challenges are provided so that users of the friction stir welding process and those investigating fabrication of other laminar composites, where joining of one or more layers is essential, might draw from the authors’ experiences discussed in this paper.
Comparative Study of Transabdominal and Transvaginal Uterine Artery Doppler Pulsatility Indices at 11–13 + 6 Weeks

Objective. The objective of this study was to compare two approaches to determine the uterine artery pulsatility index (PI) as a screening measure for preeclampsia. Methods. Comparative analysis of the PI values obtained from transabdominal and transvaginal Doppler ultrasound in 351 women with singleton pregnancies who were examined between May and June 2009 during routine morphological study and risk calculation of chromosome anomalies at 11–13 + 6 weeks of gestation. Results. The mean PI measured transabdominally was 1.83 [95% confidence interval (CI) 1.78–1.89], but when measured transvaginally it was 1.98 (95% CI 1.93–2.08) (p < 0.05). Transabdominal mean PI was observed to decrease as the crown-rump length (CRL) increased: 1.96 (95% CI 1.80–2.12) for CRL <60 mm and 1.71 (95% CI 1.56–1.87) for CRL ≥70 mm (p < 0.05). The transvaginally measured indices were 2.09 (95% CI 1.93–2.26) and 1.78 (95% CI 1.64–1.92), respectively, for the same CRL groups (p < 0.05). A weak correlation was found between the mean PI and the mean CRL using Spearman's rho correlation (–0.20 for abdominal measures and –0.21 for vaginal measures, p < 0.001). Conclusions. Transabdominal and transvaginal Doppler ultrasound measurements of the uterine artery PI were significantly different. The latter approach yielded significantly higher values than the first.
The Madding Crowd Goes to School: Myths about Crowds in Introductory Sociology Textbooks

The authors examined the crowd sections of 20 introduction to sociology textbooks, coding them for the presence of seven crowds myths—claims about crowds that have no empirical support and have been rejected by scholars in the field. The number of myths per book ranges from five to one. The authors conclude by making suggestions for rewriting these chapters and for improving the book reviewing process.
Evidence for an Immune Role on Cognition in Schizophrenia: A Systematic Review

Objective: Recent evidence has associated immune and inflammatory changes to cognitive performance in many diseases, including schizophrenia. Since this is a new research field where concepts are not yet solid and new questions and hypothesis are still arising, the present study aimed at summarizing the available clinical data associating schizophrenia, cognition and inflammation/immune function. Methods: A systematic review of the literature was made by searching the following terms in Medline: “schizophrenia or psychosis or psychotic” AND “inflamm* or immun* or cytokine or IL-* or TNF-* or kynureni* or KYNA”, AND “cognit* or attention or memory or executive function”. Results: Seventy five papers were identified using the selected terms, and seven papers were included in the review. Papers excluded focused mainly on basic research or other neuropsychiatric disorders. Conclusions: Recent findings link inflammatory markers to cognition in schizophrenia, suggesting that inflammation is associated with worst cognitive performance. Microglial activation, monoaminergic imbalance, brain abnormalities and the kynurenine pathway are possible mechanisms underlying cognitive impairment in schizophrenia. Clinical trials with addition of immunomodulatory drugs have shown promising results, opening new windows to tackle cognition in schizophrenia.
Phosphatidylinositol (4,5) Bisphosphate Controls T Cell Activation by Regulating T Cell Rigidity and Organization

Here we investigate the role of Phosphatidylinositol (4,5) bisphosphate (PIP2) in the physiological activation of primary murine T cells by antigen presenting cells (APC) by addressing two principal challenges in PIP2 biology. First, PIP2 is a regulator of cytoskeletal dynamics and a substrate for second messenger generation. The relative importance of these two processes needs to be determined. Second, PIP2 is turned over by multiple biosynthetic and metabolizing enzymes. The joint effect of these enzymes on PIP2 distributions needs to be determined with resolution in time and space. We found that T cells express four isoforms of the principal PIP2-generating enzyme phosphatidylinositol 4-phosphate 5-kinase (PIP5K) with distinct spatial and temporal characteristics. In the context of a larger systems analysis of T cell signaling, these data identify the T cell/APC interface and the T cell distal pole as sites of differential PIP2 turnover. Overexpression of different PIP5K isoforms, as corroborated by knock down and PIP2 blockade, yielded an increase in PIP2 levels combined with isoform-specific changes in the spatiotemporal distributions of accessible PIP2. It rigidified the T cell, likely by impairing the inactivation of Ezrin Moesin Radixin, delayed and diminished the clustering of the T cell receptor at the cellular interface, reduced the efficiency of T cell proximal signaling and IL-2 secretion. These effects were consistently more severe for distal PIP5K isoforms. Thus spatially constrained cytoskeletal roles of PIP2 in the control of T cell rigidity and spatiotemporal organization dominate the effects of PIP2 on T cell activation.
Use of the VITEK 2 system to identify and test the antifungal susceptibility of clinically relevant yeast species

Eleven quality control isolates (Candida albicans ATCC 64548, C. tropicalis ATCC 200956, C. glabrata ATCC 90030, C. lusitaniae ATCC 200951, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, C. dubliniensis ATCC 6330, Saccharomyces cerevisiae ATCC 9763, Cryptococcus neoformans ATCC 90012, C. gattii FIOCRUZ-CPF 60, and Trichosporon mucoides ATCC 204094) and 32 bloodstream isolates, including C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, C. guilliermondii, C. pelliculosa (Pichia anomala), C. haemulonii, C. lusitaniae, and C. kefyr were identified at the species level by the VITEK 2 system. A set of clinical isolates (32 total) were used as challenge strains to evaluate the ability of the VITEK 2 system to determine the antifungal susceptibility of yeasts compared with the CLSI and EUCAST BMD reference standards. The VITEK 2 system correctly identified 100% of the challenge strains. The identification of yeast species and the evaluation of their susceptibility profiles were performed in an automated manner by the VITEK 2 system after approximately 15 h of growth for most species of Candida. The VITEK 2 system ensures that each test is performed in a standardized manner and provides quantitative MIC results that are reproducible and accurate when compared with the BMD reference methods. This system was able to determine the MICs of amphotericin B, flucytosine, voriconazole, and fluconazole in 15 h or less for the most common clinically relevant Candida species. In addition, the VITEK 2 system could reliably identify resistance to flucytosine, voriconazole, and fluconazole and exhibits excellent quantitative and qualitative agreement with the CLSI or EUCAST broth microdilution reference methods.
The warm-cold variable in first impressions of persons.

This experiment is one of several studies of first impressions (3), the purpose of the senes being to investigate the stability of early judgments, their determinants, and the relation of such judgments to the behavior of the person making them In interpreting the data from several nonexperimental studies on the stability of first impressions. It proved to be necessary to postulate inner-observer vanables which contnbute to the impression and which remain relatively constant through time Also some evidence was obtained which directly demonstrated the existence of these variables and their nature. The present expenment was designed to determine the effects of one kind of mner-ohserver variable, specifically, expectations about the stimulus person which the observer brings to the exposure situation That prior information or labels attached to a stimulus person make a difference in observers' first impressions is almost too obvious to require demonstration The expectations resulting from such preinformation may restrict, modify, or accentuate the impressions ht will have The crucial qu^tion is What changes in percepticHi will accompany a given expectation ? Studies of stereotyping, for example, that of Katz and Braly (2), indicate that from an ethnic label sitth as "German" or "Negro," a number of perceptions follow which are culturally determined Tlw present study finds its main significance in relation to a study by Asch (1) which demonstrates that certain crucial labels can transform the entire impression of the perscm, leading to attributions which are related to the label on a broad cultural basis or even, perhaps, on an autochthonous basis Asch read to his subjects a list of adjectives which purportedly described a particular person He then asked them to characterize that person He found that the inclusion in the list of what he called central qualities, such as "warm" as exposed to "cold," produced a
Exploring middle school students' use of inscriptions in project-based science classrooms

This study explores seventh graders' use of inscriptions in a teacher-designed project-based science unit. To investigate students' learning practices during the 8-month water quality unit, we collected multiple sources of data (e.g., classroom video recordings, student artifacts, and teacher interviews) and employed analytical methods that drew from a naturalistic approach. The findings showed that throughout the unit, provided with the teachers' scaffold and social, conceptual, and material resources, the seventh graders were able to use various inscriptions (e.g., digital pictures, Web pages, and models) to demonstrate meaningful inscriptional practices such as creating and using inscriptions to make arguments, to represent conceptual understandings, and to engage in thoughtful discussions. Inscriptions and associated practices provided students with experiences and understandings about certain ways to organize, transform, and link data or scientific ideas. However, when constructing inscriptions, students did not consider how the inscriptions could serve certain reasoning purposes. In addition, more scaffolds were needed to help students use multiple inscriptions to make a coherent argument. © 2006 Wiley Periodicals, Inc. Sci Ed90:852–873, 2006
Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2Aα

Cantharidin, a natural vesicant, inhibits the activity of several PPP family phosphatases, displays antitumor activity, and induces apoptosis in many types of tumor cells. However, the molecular mechanisms underlying the antitumor activity of cantharidin are not clear. Here, dose-response studies confirm a strong correlation between the suppression of phosphatase activity and cell death. Flow cytometry analysis indicates that before apoptosis, cantharidin delays cell cycle progression following DNA replication with no apparent effect on G1-S or S-G2 phase progression. In contrast, studies with double thymidine-synchronized populations of cells indicate that cantharidin can rapidly arrest growth when added during G2 or early M phase. Immunostaining indicates that cell cycle arrest occurs before the completion of mitosis and is associated with the appearance of aberrant mitotic spindles. Live cell imaging with time-lapse microscopy shows that cantharidin disrupts the metaphase alignment of chromosomes and produces a prolonged mitotic arrest, with the onset of apoptosis occurring before the onset of anaphase. To explore the contribution of individual phosphatases, antisense oligonucleotides and small interfering RNA were developed to suppress the expression of cantharidin-sensitive phosphatases. The suppression of PP2Aα, but not PP2Aβ, is sufficient to induce metaphase arrest, during which time lagging chromosomes are observed moving between the spindle poles and the metaphase plate. Immunostaining revealed slightly abnormal, yet predominately bipolar, mitotic spindles. Nonetheless, after a 10- to 15-hour delay, the cells enter anaphase, suggesting that an additional cantharidin-sensitive phosphatase is involved in the progression from metaphase into anaphase or to prevent the onset of apoptosis in cells arrested during mitosis. [Mol Cancer Ther 2006;5(11):2727–36]
The danger hypothesis applied to idiosyncratic drug reactions

Purpose of reviewIdiosyncratic drug reactions pose a significant clinical threat and hamper drug development. The idiosyncratic nature of these reactions has made mechanistic studies exceedingly difficult, and yet without a better understanding of the mechanisms involved it is unlikely that much progress can be made in dealing with the problem. Several working hypotheses have been used to study these reactions, but none fits all of the characteristics that are observed. Borrowed from immunology, the danger hypothesis has most recently been used to explain several characteristics of these reactions. The present review describes the danger hypothesis and compares it with previous hypotheses to determine how well each fits with the observed characteristics of the reactions. Recent findingsSlow progress in the field continues and it is important to use new observations, such as identifying T cells that recognize drugs in the absence of reactive metabolite formation, to test and refine the working hypotheses. However, the development of animal models of idiosyncratic drug reactions as well as progress in basic immunology and genomics are likely to accelerate progress in this area in the near future. SummaryNo one model fits the characteristics of all idiosyncratic drug reactions; however, the danger model provides a new perspective and suggests avenues of research that have the potential to increase our ability to predict and prevent such reactions significantly.
Decision Analysis Supports the Paradigm That Indiscriminate Supplementation of Vitamin E Does More Harm than Good

Objectives—For many years, the prevailing concept was that LDL oxidation plays a central role in atherogenesis. As a consequence, supplementation of antioxidants, particularly vitamin E, became very popular. Unfortunately, however, the major randomized clinical trials have yielded disappointing results on the effects of vitamin E on both mortality and morbidity. Moreover, recent meta-analyses have concluded that vitamin E supplementation increases mortality. This conclusion has raised much criticism, most of it relating to three issues: (1) the choice of clinical trials to be included in the meta-analyses; (2) the end point of these meta-analyses (only mortality); and (3) the heterogeneity of the analyzed clinical trials with respect to both population and treatment. Our goal was to bring this controversy to an end by using a Markov-model approach, which is free of most of the limitations involved in using meta-analyses. Methods and Results—We used a Markov model to compare the vitamin E supplemented virtual cohorts with nonsupplemented cohorts derived from published randomized clinical trials that were included in at least one of the major meta-analyses. The difference between the virtual supplemented and nonsupplemented cohorts is given in terms of a composite end point denoted quality-adjusted life year (QALY). The vitamin E supplemented virtual cohort had 0.30 QALY (95%CI 0.21 to 0.39) less than the nontreated virtual cohort. Conclusions—Our study demonstrates that in terms of QALY, indiscriminate supplementation of high doses of vitamin E is not beneficial in preventing CVD. Selective supplementation of vitamin E to individuals under oxidative stress requires further investigation.
Sixteen-slice computed tomographic angiography is a reliable noninvasive screening test for clinically significant blunt cerebrovascular injuries.

BACKGROUND In light of their potential for devastating consequences, a liberalized screening approach for blunt cerebrovascular injuries (BCVI) is becoming increasingly accepted. The gold standard for diagnosis of BCVI is arteriography (ART), but noninvasive diagnostic alternatives offer clear advantages. Prospective comparative studies found that computed tomographic angiography (CTA) was unreliable in detecting BCVI. However, with advanced CTA technology, it has become more difficult to justify ART in asymptomatic patients. We implemented a liberal screening protocol for BCVI, employing 16-slice CTA. We hypothesized that CTA would detect all clinically significant BCVI. METHODS Patients undergoing computed tomography scanning for cranial or cervical trauma, as well as those with high-risk injury mechanisms or patterns, had craniocervical CTA performed. Abnormal CTA studies were confirmed with ART. Patients were followed for signs or symptoms of ischemic neurologic events. RESULTS Over an 11-month period, 331 patients underwent CTA. Eighteen (5.4%) patients had a total of 20 BCVI. There were 11 carotid and 9 vertebral artery injuries. Seven of nine (78%) vertebral injuries were associated with cervical spine fractures. Two patients who did not meet screening criteria had signs or symptoms of BCVI before CTA. No patient with normal CTA developed evidence of BCVI. CONCLUSIONS CTA detected all clinically significant injuries during this study period. Liberal screening with 16-slice CTA is appropriate and is likely to miss very few significant injuries. A multicenter trial will help to clarify risk factors and the accuracy of noninvasive diagnostic modalities.
Solitaire AB stent-assisted coiling of wide-necked intracranial aneurysms: mid-term results from the SOLARE Study.

BACKGROUND Endovascular treatment of intracranial aneurysms can be technically difficult when the neck is wide. The Solitaire AB stent (Covidien, Irvine, California), the only fully retrieved stent, assists in the coiling of wide-neck intracranial aneurysms. OBJECTIVE To evaluate the mid-term angiographic follow-up of wide-necked aneurysms treated with the Solitaire AB stent. METHODS SOLARE (SOLitaire Aneurysm Remodeling) is a consecutive, prospective study conducted in 7 European centers. A core laboratory evaluated the postoperative and mid-term (6 month ± 15 days) angiographic results by using the Raymond classification Scale. Recanalization was defined as worsening, and progressive thrombosis was defined as improvement in the Raymond scale score. RESULTS The mean width of the aneurysm sac was 7.5 mm, and the mean diameter of the aneurysm neck was 4.7 mm. Angiographic mid-term follow-up was obtained in 55 of 65 aneurysms (85.9%). Complete occlusion was achieved in 33 aneurysms (60%); a neck remnant was seen in 16 aneurysms (29.1%) and an aneurysm remnant in 6 aneurysms (10.9%). Of 55 aneurysms, recanalization was observed in 8 aneurysms (14.5%), and progressive thrombosis was observed in 17 aneurysms (30.9%). No bleeding or rebleeding was observed during the follow-up period. CONCLUSION Stent-assisted coiling of wide-necked intracranial aneurysms was found to be safe and effective with the Solitaire AB stent at 6-month follow-up. Angiographic results improve with time due to progressive thrombosis of the aneurysm.