Miracle-dz/UniFAR-FTUs huggingface dataset:
Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

Significance Nanotechnology is a promising approach for improving cancer diagnosis and treatment with reduced side effects. A key question that has emerged is: What is the ideal nanoparticle size, shape, or surface chemistry for targeting tumors? Here, we show that tumor pathophysiology and volume can significantly impact nanoparticle targeting. This finding presents a paradigm shift in nanomedicine away from identifying and using a universal nanoparticle design for cancer detection and treatment. Rather, our results suggest that future clinicians will be capable of tailoring nanoparticle designs according to the patient's tumor characteristics. This concept of “personalized nanomedicine” was tested for detection of prostate tumors and was successfully demonstrated to improve nanoparticle targeting by over 50%. Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes.
Human Cytomegalovirus Gene Expression Is Silenced by Daxx-Mediated Intrinsic Immune Defense in Model Latent Infections Established In Vitro

ABSTRACT In addition to productive lytic infections, herpesviruses such as human cytomegalovirus (HCMV) establish a reservoir of latently infected cells that permit lifelong colonization of the host. When latency is established, the viral immediate-early (IE) genes that initiate the lytic replication cycle are not expressed. HCMV IE gene expression at the start of a lytic infection is facilitated by the viral pp71 protein, which is delivered to cells by infectious viral particles. pp71 neutralizes the Daxx-mediated cellular intrinsic immune defense that silences IE gene expression by generating a repressive chromatin structure on the viral major IE promoter (MIEP). In naturally latently infected cells and in cells latently infected in vitro, the MIEP also adopts a similar silenced chromatin structure. Here we analyze the role of Daxx in quiescent HCMV infections in vitro that mimic some, but not all, of the characteristics of natural latency. We show that in these “latent-like” infections, the Daxx-mediated defense that represses viral gene expression is not disabled because pp71 and Daxx localize to different cellular compartments. We demonstrate that Daxx is required to establish quiescent HCMV infections in vitro because in cells that would normally foster the establishment of these latent-like infections, the loss of Daxx causes the lytic replication cycle to be initiated. Importantly, the lytic cycle is inefficiently completed, which results in an abortive infection. Our work demonstrates that, in certain cell types, HCMV must silence its own gene expression to establish quiescence and prevent abortive infection and that the virus usurps a Daxx-mediated cellular intrinsic immune defense mechanism to do so. This identifies Daxx as one of the likely multiple viral and cellular determinants in the pathway of HCMV quiescence in vitro, and perhaps in natural latent infections as well.
Working and Learning in a Field Excursion

This study aimed to discern sociocultural processes through which students learn in field excursions. To achieve this aim, short-term ethnographic techniques were employed to examine how undergraduate students work and enact knowledge (or knowing) during a specific field excursion in biology. The students participated in a working practice that employed research methods and came to engage with various biological phenomena over the course of their work. A three-level analysis of the students’ experiences focused on three processes that emerged: participatory appropriation, guided participation, and apprenticeship. These processes derive from advances in practice-oriented theories of knowing. Through their work in the field, the students were able to enact science autonomously; they engaged with peers and teachers in specific ways and developed new understandings about research and epistemology founded on their experiences in the field. Further discussion about the use of “practice” and “work” as analytical concepts in science education is also included.
Fast and Cost-Effective Biochemical Spectrophotometric Analysis of Solution of Insect “Blood” and Body Surface Elution

Using insect hemolymph (“blood”) and insect body surface elutions, researchers can perform rapid and cheap biochemical analyses to determine the insect’s immunology status. The authors of this publication describe a detailed methodology for a quick marking of the concentration of total proteins and evaluation of the proteolytic system activity (acid, neutral, and alkaline proteases and protease inhibitors), as well as a methodology for quick “liver” tests in insects: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and urea and glucose concentration analyses. The meaning and examples of an interpretation of the results of the presented methodology for biochemical parameter determination are described for the example of honey bees.
Long-term treatment of neuropathic pain with a 5% lidocaine medicated plaster

Background and objective The 5% lidocaine medicated plaster is a topical treatment for peripheral neuropathic pain symptoms (e.g. burning, shooting and stabbing pain) and is registered for the treatment of postherpetic neuralgia. This study examined the efficacy and tolerability of long-term treatment with the 5% lidocaine medicated plaster in patients with localized neuropathic pain conditions. Methods Twenty patients with localized neuropathic pain [postoperative neuropathic pain (n = 14); complex regional pain syndrome (n = 2); and postherpetic neuralgia (n = 4)], who had been successfully treated with 5% lidocaine medicated plaster, were followed up by telephone interview after 3 and 5 years. Questions were related to the efficacy, development of tolerance, tolerability, wear time and comfort of the plaster. Results At 3 years, 10 out of 20 (50%) initial responders were still using the plasters with no decline in analgesic efficacy. After 5 years, eight of the original 20 responders (40%) maintained treatment and continued to experience effective pain relief. The 12 responders who discontinued treatment did so because they no longer required analgesic therapy (n = 4); their health insurer refused to fund treatment (n = 2); they were lost to follow-up (n = 1); or had died from an illness unrelated to plaster treatment (n = 5). No patient discontinued because of inadequate analgesia or intolerable side effects. Reversible erythema occurred in two patients wearing the plaster for more than 16 h. There were no systemic side effects. Conclusion The 5% lidocaine medicated plaster provides sustained pain relief over long-term treatment in patients with neuropathic pain of various causes and is well tolerated.
SAR: A sentiment-aspect-region model for user preference analysis in geo-tagged reviews

Many location based services, such as FourSquare, Yelp, TripAdvisor, Google Places, etc., allow users to compose reviews or tips on points of interest (POIs), each having a geographical coordinates. These services have accumulated a large amount of such geo-tagged review data, which allows deep analysis of user preferences in POIs. This paper studies two types of user preferences to POIs: topical-region preference and category aware topical-aspect preference. We propose a unified probabilistic model to capture these two preferences simultaneously. In addition, our model is capable of capturing the interaction of different factors, including topical aspect, sentiment, and spatial information. The model can be used in a number of applications, such as POI recommendation and user recommendation, among others. In addition, the model enables us to investigate whether people like an aspect of a POI or whether people like a topical aspect of some type of POIs (e.g., bars) in a region, which offer explanation for recommendations. Experiments on real world datasets show that the model achieves significant improvement in POI recommendation and user recommendation in comparison to the state-of-the-art methods. We also propose an efficient online recommendation algorithm based on our model, which saves up to 90% computation time.
Tepid massage for febrile children: A systematic review and meta‐analysis

AIM This study aimed to examine the effect of tepid massage in febrile children comparing with other fever management. METHODS Experimental studies published in English were included; quasi-experimental research studies were also included in consideration of rare experimental studies in Korean. The search strategy sought to identify published research reports in the English language and covered all major databases up to 2016. The methodological quality of each study was assessed by 2 independent reviewers using a Scottish Intercollegiate Guidelines Network's Methodology Checklist. Means and standard deviations were used for continuous variables, and standardized mean difference was used for variables of different scales. Heterogeneity was assessed using the I2 statistics after visual reviewing with forest plots. RESULTS This study reviewed mainly the effect of tepid massage on temperature compared with the use of antipyretics, along with other adverse effects in relation with fever management. The results revealed no significant effect of tepid massage on temperature in febrile children. In addition, incidence rates of adverse effects including chills, goose pimples, and discomfort were higher in tepid massage groups. CONCLUSION This meta-analysis showed the need for re-verification of commonly used practice including the use of tepid massage and proper body temperature measurement.
When Characters Impact on Dubbing: The Role of Sexual Stereotypes on Voice Actor/Actress’ Preferences

Dubbing is a procedure through which an original actor’s voice is replaced with that of a voice actor, usually speaking a different language. Dubbing is not only an adaptation to language but also to cultural beliefs. Across two studies, we analyzed how some Italian participants would prefer a television series’ character to sound. In Study 1, participants read a male/female character description that was manipulated according to gender and sexual stereotypes in order to be masculine, feminine, or gender-neutral. Next, participants were asked to indicate their preference for three voice actors/actresses who sounded heterosexual, gay/lesbian, or ambivalent. Study 2 tested the interplay between a character’s description and the voice of the English-speaking (gay/lesbian vs. heterosexual sounding) actor/actress who played the role in the original television series on dubbing preferences. The results of both studies showed that a character’s description affected dubbing preferences. Participants preferred the gay/lesbian-sounding voice actor/actress to the counter-stereotypical character (i.e., a feminine man or a masculine woman) and the heterosexual-sounding voice actor/actress to the stereotypical character. Interestingly, at least for male targets, the original actor’s voice itself affected the preference for voice actors in the same way. This work suggests that dubbing can maintain and reinforce stereotypes.
The Influence of Heel Counter Rigidity on Rearfoot Motion during Running

The purpose of the current study was to examine rearfoot motion using three-dimensional recording techniques and shoes with varying heel counter rigidity. The results showed that only the more rigid shoes tended to create significant differences between calcaneal and shoe heel eversion during ground contact, except close to heel-strike. The rigid shoe thus resisted eversional forces. The calcaneus, however, was not prevented from slipping within the shoe and from everting as much or nearly as fast as in a shoe with a more flexible heel counter. In order to simulate two-dimensional recording techniques commonly used in rearfoot studies, a two-dimensional reduction of the original three-dimensional angular data was performed. However, the results produced were similar if torsional movement between the foot and shoe was ignored.
The use of PPI is associated with spontaneous bacterial peritonitis in cirrhotic patients of different ethnic groups : a meta-analysis

Background: Spontaneous bacterial peritonitis (SBP) is one of the most serious complications of cirrhotic patients. A few studies have shown that use of proton pump inhibitors (PPI) may increase the risk of occurrence of SBP in cirrhotic patients. However, controversial results have been obtained in the last decades. Therefore, the purpose of our analysis was to investigate the relationship between the risk of development of Spontaneous bacterial peritonitis (SBP) and the administration of proton pump inhibitors (PPI) in cirrhotic patients. Methods: Observational studies, about the relationship between PPI therapy and SBP in cirrhotic patients, were searched in PubMed, Medline, Embase, Web of Knowledge and other databases, and retrieval time ended in Jun 2015. Data from the identified studies were evaluated by odds ratios (ORs) and 95% confidence interval (CI) using traditional meta-analytic techniques. Results: Eleven studies (n = 4567 patients) met the inclusion criteria. The results showed that the risk of development of SBP significantly increased (OR = 2.04, 95% CI 1.56-2.69, P < 0.00001) in cirrhotic patients with PPI. The fixed effect model was used because of low heterogeneity, P < 0.1 and I2 = 44%. Subgroup analysis was performed in different study regions. The risk of developing SBP in cirrhotic patients with PPI treatment was significantly increased (OR = 2.22, 95% CI 1.72-2.87, P < 0.0001; OR = 1.70, 95% CI 0.70-4.13, P = 0.24; OR = 1.99, 95% CI 1.19-3.32, P = 0.009) in Asian, European, and American patients. Moderate heterogeneity existed in Euro-American patients. Conclusion: There was a significant correlation between the development of SBP and the use of PPI in cirrhotic patients. Therefore, clinicians should be aware of the indications of PPI, and use PPI cautiously in these patients. Further research need to clarify the correlation between the type, dose and course of treatment of PPI and the development of SBP in cirrhotic patients.
Pinus Roxburghii essential oil anticancer activity and chemical composition evaluation

The present study was conducted to appraise the anticancer activity of Pinus roxburghii essential oil along with chemical composition evaluation. MTT assay revealed cytotoxicity induction in colon, leukemia, multiple myeloma, pancreatic, head and neck and lung cancer cells exposed to essential oil. Cancer cell death was also observed through live/dead cell viability assay and FACS analysis. Apoptosis induced by essential oil was confirmed by cleavage of PARP and caspase-3 that suppressed the colony-forming ability of tumor cells and 50 % inhibition occurred at a dose of 25 μg/mL. Moreover, essential oil inhibited the activation of inflammatory transcription factor NF-κB and inhibited expression of NF-κB regulated gene products linked to cell survival (survivin, c-FLIP, Bcl-2, Bcl-xL, c-Myc, c-IAP2), proliferation (Cyclin D1) and metastasis (MMP-9). P. roxburghii essential oil has considerable anticancer activity and could be used as anticancer agent, which needs further investigation to identify and purify the bioactive compounds followed by in vivo studies.
Gender Differences in a Dutch Forensic Sample of Severe Violent Offenders

ABSTRACT Awareness is growing that the knowledge we have on male offenders, to a large extent, may not be applicable to female offenders. The current study was performed in a Dutch forensic assessment center. The sample consisted of 140 female offenders and 140 male matched-controls. The study focused on the mental disorders, psychological factors, and crime-related variables of female offenders in comparison to those of their male counterparts. The results of this study indicate that female offenders differ from male offenders on various variables. More specifically, female offenders were more often depressed, more often had traits of a borderline personality, were more often sexually and physically abused and emotionally neglected, showed more self-harming behavior, and had a lower self-esteem. These results suggest that more research on gender differences in offenders is needed to provide insight in how a gender specific forensic treatment should be established.
Anti-angiogenic VEGFAxxxb transcripts are not expressed in the medio-basal hypothalamus of the seasonal sheep

This study investigated Vegfa expression in the pars tuberalis (PT) of the pituitary and medio-basal hypothalamus (MBH) of sheep, across seasons and reproductive states. It has recently been proposed that season impacts alternative splicing of Vegfa mRNA in the PT, which shifts the balance between angiogenic VEGFAxxx and anti-angiogenic VEGFAxxxb isoforms (with xxx the number of amino acids of the mature VEGFA proteins) to modulate seasonal breeding. Here, we used various RT-PCR methodologies and analysis of RNAseq datasets to investigate seasonal variation in expression and splicing of the ovine Vegfa gene. Collectively, we identify 5 different transcripts for Vegfa within the ewe PT/MBH, which correspond to splicing events previously described in mouse and human. All identified transcripts encode angiogenic VEGFAxxx isoforms, with no evidence for alternative splicing within exon 8. These findings led us to investigate in detail how “Vegfaxxxb-like” PCR products could be generated by RT-PCR and misidentified as endogenous transcripts, in sheep and human HEK293 cells. In conclusion, our findings do not support the existence of anti-angiogenic VEGFAxxxb isoforms in the ovine PT/MBH and shed new light on the interpretation of prior studies, which claimed to identify Vegfaxxxb isoforms by RT-PCR.
Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5’ ends of a DSB. For example, loss of 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single cell assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living S. pombe cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that “rewiring” of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.
Methodological considerations for investigating expert interceptive skill in in situ settings

This article discusses some key methodological issues related to conducting complex whole body in situ studies involving high-speed interceptive timing skills. The methodological issues that are discussed include the use of object projection machines versus live opponents, the use of multiple opponents (actors), presentation of stimulus information, trial numbers for participants, participant group sample sizes, small-scale comparisons across expertise groups and individuals, as well as timing and accuracy measures. The position argued in each of the foregoing methodological issues is formulated from the theoretical framework of representative task design, where experimental design needs to reflect (and accommodate) the key constraints of the real-world game setting that the researcher intends relevant findings to be generalized. To help conceptualization, a diagram is included showing different methodologies, their degree of representative task design and their respective generalization to the game setting. Collectively, it is hoped that this article will assist researchers in the design, implementation and reporting of in situ studies in expertise and motor skill learning in sport.
Using the Quadruple Aim Framework to Measure Impact of Heath Technology Implementation: A Case Study of eConsult

Background: Health technology solutions are too often implemented without a true understanding of the system-level problem they seek to address, resulting in excessive costs, poor adoption, ineffectiveness, and ultimately failure. Before implementing or adopting health care innovations, stakeholders should complete a thorough assessment to ensure effectiveness and value. In this article, we describe how to evaluate the impact of a health technology innovation through the 4 dimensions of care outlined by the Quadruple Aim Framework, using our experience with the Champlain Building Access to Specialists through eConsultation (BASE) eConsult service as a case example. Methods: A descriptive overview of data was collected between April 1, 2011, and August 31, 2017, using 4 dimensions of care outlined by the Quadruple Aim Framework: patient experience, provider experience, costs, and population health. Findings were drawn from use data, primary care provider closeout surveys, surveys/interviews with patients and provider, and costing data. Results: Overall, patients have received access to specialist advice within days and find the advice useful in 86% of cases. Provider experience is very positive, with satisfaction ratings of high/very high value in 94% of cases. The service cost a weighted average of $47.35/case, compared with $133.60/case for traditional referrals. In total, 1,299 primary care providers have enrolled in the service, completing 28,838 cases since 2011. Monthly case volumes have grown from an average of 13 cases/month in 2011 to 969 cases/month in 2016. Conclusions: The eConsult service has been widely adopted in our region and is currently expanding to new jurisdictions across Canada. However, although we successfully demonstrated eConsult's impact on patient experience, provider satisfaction, and reducing costs, we met several challenges in evaluating its impact on population health. More work is needed to evaluate eConsult's impact on key population health metrics (eg, mortality, morbidity, and system use). Efforts to conduct such evaluations are underway.