Miracle-dz/UniFAR-FTUs huggingface dataset:
HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy

Mutations in the HER2 kinase domain have been identified in human clinical lung cancer specimens. Here we demonstrate that inducible expression of the most common HER2 mutant (HER2YVMA) in mouse lung epithelium causes invasive adenosquamous carcinomas restricted to proximal and distal bronchioles. Continuous expression of HER2YVMA is essential for tumor maintenance, suggesting a key role for HER2 in lung adenosquamous tumorigenesis. Preclinical studies assessing the in vivo effect of erlotinib, trastuzumab, BIBW2992, and/or rapamycin on HER2YVMA transgenic mice or H1781 xenografts with documented tumor burden revealed that the combination of BIBW2992 and rapamycin is the most effective treatment paradigm causing significant tumor shrinkage. Immunohistochemical analysis of lung tumors treated with BIBW2992 and rapamycin combination revealed decreased phosphorylation levels for proteins in both upstream and downstream arms of MAPK and Akt/mTOR signaling axes, indicating inhibition of these pathways. Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted.
Racing Against the Clock: Internal Medicine Residents' Time Spent On Electronic Health Records.

BACKGROUND Since the late 1980s, resident physicians have spent increasing amounts of time on electronic health record (EHR) data entry and retrieval. Objective longitudinal data measuring time spent on the EHR are lacking. OBJECTIVE We sought to quantify the time actually spent using the EHR by all first-year internal medicine residents in a single program (N = 41). METHODS Active EHR usage data were collected from the audit logs for May, July, and October 2014 and January 2015. Per recommendations from our EHR vendor (Cerner Corporation), active EHR usage time was defined as more than 15 keystrokes, or 3 mouse clicks, or 1700 "mouse miles" per minute. Active EHR usage time was tallied for each patient chart viewed each day and termed an electronic patient record encounter (EPRE). RESULTS In 4 months, 41 interns accumulated 18,322 hours of active EHR usage in more than 33,733 EPREs. Each intern spent on average 112 hours per month on 206 EPREs. Interns spent more time in July compared to January (41 minutes versus 30 minutes per EPRE, P < .001). Time spent on the EHR in January echoed that of the previous May (30 minutes versus 29 minutes, P = .40). CONCLUSIONS First-year residents spent a significant amount of time actively using the EHR, achieving maximal proficiency on or before January of the academic year. Decreased time spent on the EHR may reflect greater familiarity with the EHR, growing EHR efficiencies, or other factors.
Cisplatin restores p53 function and enhances the radiosensitivity in HPV16 E6 containing SiHa cells

Most HPV‐positive cervical cancer cells possess wild type p53 gene, but its normal p53 functions are disrupted by expression of HPVs E6. Treatment with 0–20 μM cisplatin for 24 h in HPV16 E6 containing SiHa cells suppressed E6 mRNA, reduced E6 protein, and restored p53 expression in dose‐dependent manners. Dual‐parameter flow cytometric analysis indicated that sub‐G1 apoptotic cells, but not necrotic cells were the major species for cisplatin‐induced cytotoxicity in SiHa cells. After 0–10 μM cisplatin treatment, slightly more apoptotic cells appeared from SiHa cells than those from dominant negative p53‐transfected SiHa cells. There was no different ionizing radiation (IR)‐induced apoptosis in these two different cells. On the other hand, cisplatin enhanced more IR‐induced sub‐G1 apoptosis in SiHa than mp53‐SiHa cells. These accompanied with prolonged p53 restoration in irradiated‐SiHa cells after 24 h cisplatin treatment and thereafter. In contrast, it was not found in cells after irradiation alone. Similar results were also shown in Mdm2 expression in SiHa cells after combined treatment. Therefore, cisplatin restored p53 expression and prolonged IR‐induced p53 restoration would be possible candidates to response more sub‐G1 apoptosis in irradiated SiHa cells. These results provided another new explanation on cisplatin sensitizing radiotherapy for HPV16 E6 containing cancer cells. © 2004 Wiley‐Liss, Inc.
Fluency and belief bias in deductive reasoning: new indices for old effects

Models based on signal detection theory (SDT) have occupied a prominent role in domains such as perception, categorization, and memory. Recent work by Dube et al. (2010) suggests that the framework may also offer important insights in the domain of deductive reasoning. Belief bias in reasoning has traditionally been examined using indices based on raw endorsement rates—indices that critics have claimed are highly problematic. We discuss a new set of SDT indices fit for the investigation belief bias and apply them to new data examining the effect of perceptual disfluency on belief bias in syllogisms. In contrast to the traditional approach, the SDT indices do not violate important statistical assumptions, resulting in a decreased Type 1 error rate. Based on analyses using these novel indices we demonstrate that perceptual disfluency leads to decreased reasoning accuracy, contrary to predictions. Disfluency also appears to eliminate the typical link found between cognitive ability and the effect of beliefs on accuracy. Finally, replicating previous work, we demonstrate that cognitive ability leads to an increase in reasoning accuracy and a decrease in the response bias component of belief bias.
The Role of ICT in Office Work Breaks

Break activities -- deliberate and unexpected -- are common throughout the working day, playing an important role in the wellbeing of workers. This paper investigates the role of increasingly pervasive ICT in creating new opportunities for breaks at work, what impact the technology has on management of boundaries at work, and the effects these changes have on personal wellbeing. We present a study of the routines of office-workers, where we used images from participants' work-days to prompt and contextualize interviews with them. Analysis of coded photographs and interview data makes three contributions: an account of ubiquitous ICT creating new forms of micro-breaks, including the opportunity to employ previously wasted time; a description of the ways in which staff increasingly bring "home to work"; and a discussion of the emergence of "screen guilt". We evaluate our findings in relation to previous studies, and leave three research implications and questions for future work in this domain.
Prevalence of Metabolic Syndrome among Iranian Population: A Systematic Review and Meta-analysis

Background: Metabolic syndrome (MetS) is the major risk factor for development of type 2 diabetes and cardiovascular diseases in different populations. The aim of this study was to evaluate the prevalence of MetS among Iranian population. Methods: Thirty-four cross-sectional studies were analyzed with a sample of 83227 people. National and international English electronic databases (PubMed, Google scholar, Web of Science, Science Direct, and Scopus) and Persian language databases (SID, Medlib, Iran medex, Magiran, Medlib, and IranDoc) were used to search the articles published on MetS in Iranian population from Jan 2005 to May 2016. The MetS diagnosis was performed according to the ATP-III, NCEP/ATP-III, IDF and WHO criteria. Results: The overall weighted prevalence of MetS was 31% (95% CI: 28–35). According to ATP III criteria, total and gender-stratified prevalence of MetS in women and men were 29% (95% CI: 22–36), 37% (95% CI: 26–48) and 29% (95% CI: 23–36), respectively. Total prevalence of MetS based on NCEP/ATP III criteria was 29% (95% CI: 24–35) that the prevalence was 24% (95% CI: 18–30) and 35% (95% CI: 25–44) in men and women, respectively. According to the IDF and WHO criteria, total prevalence of MetS were 38% (95% CI: 32–43) and 30% (95% CI: 7–53), respectively. Conclusion: The findings demonstrate an emerging high prevalence of MetS in total and in particular among Iranian women population. Therefore, to minimize the risk of cardiovascular events in Iranian population, screening and early detection of risk factors for MetS are required.
High-resolution Immunocytochemistry of Noncollagenous Matrix Proteins in Rat Mandibles Processed with Microwave Irradiation

The mineral phase in calcified tissues represents an additional factor to be considered during their preservation for ultrastructural analyses. Microwave (MW) irradiation has been shown to facilitate fixative penetration and to improve structural preservation and immunolabeling in a variety of soft tissues. The aim of the present study was to determine whether MW processing could offer similar advantages for hard tissues. Rat hemimandibles were immersed in 4% formaldehyde + 0.1% glutaraldehyde buffered with 0.1 M sodium cacodylate, pH 7.2, and exposed to MWs for three periods of 5 min at temperatures not exceeding 37C. They were then decalcified in 4.13% EDTA, pH 7.2, for 15 hr, also under MW irradiation. Osmicated and non-osmicated samples were dehydrated in graded concentrations of ethanol and embedded in LR White resin. Sections of incisor, molars, and alveolar bone were processed for postembedding colloidal gold immunolabeling using antibodies against ameloblastin, amelogenin, bone sialoprotein, or osteopontin. Ultrastructural preservation of tissues was in most cases comparable to that obtained by perfusion-fixation, and there was no difference in distribution of labeling with those previously reported for the antibodies used. However, the immunoreactivities obtained were generally more intense, particularly at early stages of tooth formation. Amelogenin was abundant between differentiating ameloblasts and labeling for osteopontin appeared over the Golgi apparatus of odontoblasts after initiation of dentine mineralization. We conclude that MW irradiation represents a simple method that can accelerate the processing of calcified tissues while yielding good structural preservation and antigen retention. (J Histochem Cytochem 49:1099–1109, 2001)
Overdiagnosis in Mammographic Screening for Breast Cancer in Europe: A Literature Review

Objectives Overdiagnosis, the detection through screening of a breast cancer that would never have been identified in the lifetime of the woman, is an adverse outcome of screening. We aimed to determine an estimate range for overdiagnosis of breast cancer in European mammographic service screening programmes. Methods We conducted a literature review of observational studies that provided estimates of breast cancer overdiagnosis in European population-based mammographic screening programmes. Studies were classified according to the presence and the type of adjustment for breast cancer risk (data, model and covariates used), and for lead time (statistical adjustment or compensatory drop). We expressed estimates of overdiagnosis from each study as a percentage of the expected incidence in the absence of screening, even if the variability in the age range of the denominator could not be removed. Estimates including carcinoma in situ were considered when available. Results There were 13 primary studies reporting 16 estimates of overdiagnosis in seven European countries (the Netherlands, Italy, Norway, Sweden, Denmark, UK and Spain). Unadjusted estimates ranged from 0% to 54%. Reported estimates adjusted for breast cancer risk and lead time were 2.8% in the Netherlands, 4.6% and 1.0% in Italy, 7.0% in Denmark and 10% and 3.3% in England and Wales. Conclusions The most plausible estimates of overdiagnosis range from 1% to 10%. Substantially higher estimates of overdiagnosis reported in the literature are due to the lack of adjustment for breast cancer risk and/or lead time.
Anchoring Revisited: The Role of the Comparative Question

When people estimate a numeric value after judging whether it is larger or smaller than a high or low anchor value (comparative question), estimates are biased in the direction of the anchor. One explanation for this anchoring effect is that people selectively access knowledge consistent with the anchor value as part of a positive test strategy. Two studies (total N = 184) supported the alternative explanation that people access knowledge consistent with their own answer to the comparative question. Specifically, anchoring effects emerged when the answer to the comparative question was unexpected (lower than the low anchor or higher than the high anchor). For expected answers (lower than the high anchor or higher than the low anchor), however, anchoring effects were attenuated or reversed. The anchor value itself was almost never reported as an absolute estimate.
Following Your "Friend": Social Media and the Strength of Adolescents' Parasocial Relationships with Media Personae

Social media have permeated the lives of adolescents and may be altering the way that teens engage with their favorite media celebrities and characters. This study surveyed 316 adolescents to examine the relationship between social media surveillance and the strength of adolescents' parasocial relationships (PSRs) with media personae they follow on social media. Results indicated a significant positive relationship between exposure to media personae on Twitter and strength of PSRs. Adolescents who had experienced social interactions with their favorite media personae on Twitter in the form of retweets or responses to tweets had stronger PSRs than adolescents who had no such interactions. The realism of the media personae did not moderate findings as expected. The findings suggest that Twitter provides intimate glimpses into the personal lives of media personae that increase audiences' feelings of connectedness to those celebrities and characters, an important finding given that teens are more likely to learn from media personae with whom they have PSRs.
An in vitro model for characterizing the post‐migratory cranial neural crest cells of the first branchial arch

The cranial neural crest (CNC) is a transient cell population that originates at the crest of the neural fold and gives rise to multiple cell types during craniofacial development. Traditionally, researchers have used tissue explants, such as the neural tube, to obtain primary neural crest cells for their studies. However, this approach has inevitably resulted in simultaneous isolation of neural and non‐neural crest cells as both of these cells migrate away from tissue explants. Using the Wnt1‐Cre/R26R mouse model, we have obtained a pure population of neural crest cells and established a primary CNC cell culture system in which the cell culture medium best supports the proliferation of E10.5 first branchial arch CNC cells and maintains these cells in their undifferentiated state. Differentiation of CNC cells can be initiated by switching to a differentiation medium. In this model, cultured CNC cells can give rise to neurons, glial cells, osteoblasts, and other cell types, faithfully mimicking the differentiation process of the post‐migratory CNC cells in vivo. Taken together, our study shows that the Wnt1‐Cre/R26R mouse first branchial arch provides an excellent model for obtaining post‐migratory neural crest cells free of any mesodermal contaminants. The cultured neural crest cells are under sustained proliferative, undifferentiated, or lineage‐enhanced conditions, hence, serving as a tool for the investigation of the regulatory mechanism of CNC cell fate determination in normal and abnormal craniofacial development. Developmental Dynamics 235:1433–1440, 2006. © 2005 Wiley‐Liss, Inc.
Genomic Signal Processing Methods for Computation of Alignment-Free Distances from DNA Sequences

Genomic signal processing (GSP) refers to the use of digital signal processing (DSP) tools for analyzing genomic data such as DNA sequences. A possible application of GSP that has not been fully explored is the computation of the distance between a pair of sequences. In this work we present GAFD, a novel GSP alignment-free distance computation method. We introduce a DNA sequence-to-signal mapping function based on the employment of doublet values, which increases the number of possible amplitude values for the generated signal. Additionally, we explore the use of three DSP distance metrics as descriptors for categorizing DNA signal fragments. Our results indicate the feasibility of employing GAFD for computing sequence distances and the use of descriptors for characterizing DNA fragments.
European adults’ physical activity socio-demographic correlates: a cross-sectional study from the European Social Survey

Background. From a public health perspective, the study of socio-demographic factors related to physical activity is important in order to identify subgroups for intervention programs. Objective. This study aimed to identify the prevalence of, and the socio-demographic correlates related to, the achievement of recommended physical activity levels. Methods. Using data from the European Social Survey round 6, physical activity and socio-demographic characteristics were collected, in 2012, from 39,278 European adults (18,272 men, 21,006 women), aged 18–65 years, from 28 countries. The question of meeting physical activity guidelines was assessed using World Health Organization criteria. Results. A total of 64.50% (63.36% men, 66.49% women) attained physical activity recommended levels. The likelihood of attaining physical activity recommendations was higher in the 55–64 years age group (men: OR = 1.22, p < 0.05; women: OR = 1.66, p < 0.001), among those who had secondary education (men: OR = 1.28, p < 0.01; women: OR = 1.26, p < 0.05), among those who lived in rural areas (men: OR = 1.20, p < 0.001; women: OR = 1.10, p < 0.05), and among those who had three or more people living at home (men: OR = 1.40, p < 0.001; women: OR = 1.43, p < 0.001). On the other hand, attaining physical activity recommendations was negatively associated with being unemployed (men: OR = 0.70, p < 0.001; women: OR = 0.87, p < 0.05), being a student (OR = 0.56, p < 0.001; women: OR = 0.64, p < 0.01), being a retired person (men: OR = 0.86, p < 0.05) and with having a higher household income (OR = 0.80, p < 0.001; women: OR = 0.81, p < 0.01). Conclusions. This research helped clarify that, as the promotion of physical activity is critical to sustain health and prevent disease, socio-demographic factors are important to consider when planning the increase of physical activity.
COMBINED INTRAVITREAL BEVACIZUMAB INJECTION AND ZONE I SPARING LASER PHOTOCOAGULATION IN PATIENTS WITH ZONE I RETINOPATHY OF PREMATURITY

Purpose: To investigate the anatomical outcome of combined intravitreal bevacizumab injection and Zone I sparing laser ablation in patients with Type 1 retinopathy of prematurity in Zone I. Methods: The medical records of consecutive 18 eyes of 10 infants, who underwent combined intravitreal bevacizumab (0.25 mg) injection and Zone I sparing laser ablation for the treatment of Type 1 retinopathy of prematurity in Zone I, were retrospectively reviewed. Laser photocoagulation was performed on the avascular retina anterior to the margin of Zone I extending to the ora serrata. Anatomical outcomes including progression to stage 4/5, macular changes, and vitreous organization were reviewed. Results: The mean gestational age at birth and the birth weight of included patients were 24.0 weeks and 628 g, respectively. The timing of bevacizumab injection ranged from postmenstrual age 33+2 to 35 weeks (mean, 34.3 weeks). Postmenstrual age at last follow-up ranged from 74+6 to 107+1 weeks (mean, 83.6 weeks). All 18 eyes demonstrated prompt regression of neovascular pathology and plus disease without recurrence. Previously avascular Zone I retina was vascularized in all eyes after the treatment. All eyes showed excellent anatomical outcome with intact macula, but one eye showed mild vitreous organization above the vascular/avascular junction. Conclusion: Combined intravitreal bevacizumab injection and Zone I sparing laser ablation for Type 1 retinopathy of prematurity in Zone I seem to be effective treatment options. Possible advantages include lower dose of anti–vascular endothelial growth factor, less recurrence than monotherapy, and preservation of central visual field.
An Expectation Maximization Approach to Pronoun Resolution

We propose an unsupervised Expectation Maximization approach to pronoun resolution. The system learns from a fixed list of potential antecedents for each pronoun. We show that unsupervised learning is possible in this context, as the performance of our system is comparable to supervised methods. Our results indicate that a probabilistic gender/number model, determined automatically from unlabeled text, is a powerful feature for this task.
Emergence of Drug Resistance Mutations in Human Immunodeficiency Virus Type 2-Infected Subjects Undergoing Antiretroviral Therapy

ABSTRACT The reverse transcriptase (RT) and protease genes from 12 human immunodeficiency virus type 2 (HIV-2)-infected individuals who had been exposed to antiretroviral drugs for longer than 6 months were examined for the presence of mutations which could be involved in drug resistance. Four individuals carried virus genotypes with amino acid substitutions potentially associated with resistance to nucleoside analogues: two at codon 70 (K→R) and two at codon 184 (M→V). Moreover, the latter two patients harbored a codon Q151M mutation which is associated to multidrug resistance in HIV-1, and one of these subjects carried some of the typically linked mutations at codons 65 and 69. With regard to the protease inhibitors, substitutions associated with resistance to protease inhibitors at codon 46 were observed in all individuals. Moreover, minor resistance mutations, as well as new ones of unknown meaning, were often seen in the protease gene. In conclusion, amino acid changes in the HIV-2 RT and protease genes which could be associated with drug resistance seem to occur at positions identical to those for HIV-1.
A CMOS Single-Differential LNA and current bleeding CMOS mixer for GPS Receivers

This work presents a low noise amplifier (LNA) and mixer for 1558–1578 MHz Global Position System (GPS). The LNA uses cascode structure to eliminate the Miller effect. Also the next stage, the double-balanced Gilbert cell mixer is accomplished for good performance such as isolation. We suggest a Single-Differential LNA mode which has enough gain and two differential outputs. The LNA and Mixer are integrated together on a chip in 0. 18µm CMOS technology. The conversion gain of LNA and Mixer is 26 dB when one IF port is terminated to 50Ω. The 1dB compression point is −26 dBm. NF for LNA and Mixer is 4.3 dB. The total chip area is 530µm*500µm. The two circuit consumes current about 10 mA. The main achievement of this design is that we get low noise, high gain, and good linearity under low power.