Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of E2F-dependent transcription by the mouse cytomegalovirus M117 protein affects the viral host range

Cytomegaloviruses (CMVs) have a highly restricted host range as they replicate only in cells of their own or closely related species. To date, the molecular mechanisms underlying the CMV host restriction remain poorly understood. However, it has been shown that mouse cytomegalovirus (MCMV) can be adapted to human cells and that adaptation goes along with adaptive mutations in several viral genes. In this study, we identify MCMV M117 as a novel host range determinant. Mutations in this gene enable the virus to cross the species barrier and replicate in human RPE-1 cells. We show that the M117 protein is expressed with early kinetics, localizes to viral replication compartments, and contributes to the inhibition of cellular DNA synthesis. Mechanistically, M117 interacts with members of the E2F transcription factor family and induces E2F target gene expression in murine and human cells. While the N-terminal part of M117 mediates E2F interaction, the C-terminal part mediates self-interaction. Both parts are required for the activation of E2F-dependent transcription. We further show that M117 is dispensable for viral replication in cultured mouse fibroblasts and endothelial cells, but is required for colonization of mouse salivary glands in vivo. Conversely, inactivation of M117 or pharmacological inhibition of E2F facilitates MCMV replication in human RPE-1 cells, whereas replacement of M117 by adenovirus E4orf6/7, a known E2F activator, prevents it. These results indicate that E2F activation is detrimental for MCMV replication in human cells. In summary, this study identifies MCMV M117 as a novel E2F activator that functions as a host range determinant by precluding MCMV replication in human cells.
Plumbagin induces autophagy and apoptosis of SMMC‐7721 cells in vitro and in vivo

Plumbagin (PL), an active naphthoquinone compound, has been demonstrated to be a potential anticancer agent. However, the underlying anticancer mechanism is not fully understood. In this study, the human hepatocellular carcinoma (HCC) SMMC‐7721 cell line was studied in an in vitro model. The cell proliferation was inhibited by PL in a dose‐ and time‐dependent manner. Electron microscopy, acridine orange staining, and immunofluorescence were used to evaluate autophagosome formation and LC3 protein expression in PL‐treated SMMC‐7721 cells. Real‐time polymerase chain reaction and Western blot showed that PL treatment suppressed the expression of apoptosis and autophagy factors (LC3, Beclin1, Atg7, and Atg5), which are associated with tumor apoptosis and autophagy in SMMC‐7721 cells. In the study of in vitro tumor nude mouse models, PL can inhibit tumor growth. Cell apoptosis and autophagy of the transplanted tumors were evaluated by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling staining, and Western blot. In addition, in the in vivo studies of HCC cells, we found that pretreatment with the autophagy inhibitor 3‐methyladenine blocked the formation of apoptosis induced by PL. In contrast, administration of the apoptosis inhibitor Z‐VAD did not affect PL‐induced autophagy. Taken together, our findings strongly suggest that PL is a promising drug with significant antitumor activity in HCC.
Satietogenic Protein from Tamarind Seeds Decreases Food Intake, Leptin Plasma and CCK-1r Gene Expression in Obese Wistar Rats

Objective: This study evaluated the effect of a protein, the isolated Trypsin Inhibitor (TTI) from Tamarindus indica L. seed, as a CCK secretagogue and its action upon food intake and leptin in obese Wistar rats. Methods: Three groups of obese rats were fed 10 days one of the following diets: Standard diet (Labina®) + water; High Glycemic Index and Load (HGLI) diet + water or HGLI diet + TTI. Lean animals were fed the standard diet for the 10 days. Food intake, zoometric measurements, plasma CCK, plasma leptin, relative mRNA expression of intestinal CCK-related genes, and expression of the ob gene in subcutaneous adipose tissue were assessed. Results: TTI decreased food intake but did not increase plasma CCK in obese animals. On the other hand, TTI treatment decreased CCK-1R gene expression in obese animals compared with the obese group with no treatment (p = 0.027). Obese animals treated with TTI presented lower plasma leptin than the non-treated obese animals. Conclusion: We suggest that TTI by decreasing plasma leptin may improve CCK action, regardless of its increase in plasma from obese rats, since food intake was lowest.
Investigating the common set of acoustic parameters in sexual orientation groups: A voice averaging approach

While the perception of sexual orientation in voices often relies on stereotypes, it is unclear whether speech stereotypes and accurate perceptions of sexual orientation are each based on acoustic cues common to speakers of a given group. We ask if the stereotypical belief, that members of the same sexual orientation group share similar acoustic patterns, is accurate to some degree. To address this issue, we are the first to use a novel voice morphing technique to create voice averages from voices that represent extremes of a given sexual orientation group either in terms of actual or perceived sexual orientation. Importantly, averaging preserves only those acoustic cues shared by the original speakers. 144 German listeners judged the sexual orientation of twelve natural-sounding sentence stimuli, each representing an average of five original utterances. Half of the averages were based on targets’ self-ratings of sexual orientation: On a 7-point Kinsey-like scale, we selected targets who were most typical for a certain sexual orientation group according to their self-identifications. The other half were based on extreme ratings by others (i.e., on speech-related sexual-orientation stereotypes). Listeners judged sexual orientation from the voice averages with above-chance accuracy suggesting 1) that the perception of actual and stereotypical sexual orientation, respectively, are based on acoustic cues shared by speakers of the same group, and 2) that the stereotypical belief that members of the same sexual orientation group share similar acoustic patterns is accurate to some degree. Mean fundamental frequency and other common acoustic parameters showed systematic variation depending on speaker gender and sexual orientation. Effects of sexual orientation were more pronounced for stereotypical voice averages than for those based on speakers’ self-ratings, suggesting that sexual-orientation stereotypes exaggerate even those differences present in the most salient groups of speakers. Implications of our findings for stereotyping and discrimination are discussed.
Vaginal examination and fear of childbirth

10. Mifsud W, Sebire NJ. Placental pathology in earlyonset and lateonset fetal growth restriction. Fetal Diagn Ther 2014; 36: 117–128. 11. Oros D, Figueras F, Cruz-Martinez R et al. Longitudinal changes in uterine, umbilical and fetal cerebral Doppler indices in lateonset smallforgestational age fetuses. Ultrasound Obstet Gynecol 2011; 37: 191–195. 12. Gardosi J, Kady SM, McGeown P et al. Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study. BMJ 2005; 331: 1113–1117.
Comprehensive Assessment of Didactic Curriculum and Career Interest in Infectious Diseases Among Graduating United States Pharmacy Students

Abstract Background The growing need for clinicians with antimicrobial stewardship (AS) skills has resulted in an examination of educational methods for pharmacy and medical learners. This study explores characteristics associated with student assessment of didactic infectious diseases (ID) education quality and variables associated with a career interest in ID and/or AS. Methods Infectious diseases faculty from US pharmacy schools were sent a 15-question survey in September 2017. Faculty members e-mailed the survey link to graduating pharmacy students. Results Participants from 29 pharmacy schools, representing 21 states, resulted in 537 student responses. Quality of ID didactic education was rated as Very Good by 41%, Good by 40%, Acceptable by 14%, and Poor by 4% of participants. The mean number of faculty-provided learning resources differed by quality rating and was significantly associated with perceived educational needs. Infectious diseases was identified as a career interest by 29% of students. These students more frequently rated their ID didactic education as Very Good (52% vs 37%, P < .01) and were more likely to become interested in ID during or after it was taught in pharmacy school (39% vs 21%, P < .01). Conclusions In this cohort of graduating pharmacy students, the perceived quality of didactic ID education was associated with a career interest in ID and/or AS. Factors associated with quality of education were quantity and quality of faculty-provided resources. Increasing the quality of the didactic ID curriculum has potential to increase interest in ID/AS careers among pharmacy students.
LSTM-Based ECG Classification for Continuous Monitoring on Personal Wearable Devices

<italic>Objective</italic>: A novel electrocardiogram (ECG) classification algorithm is proposed for continuous cardiac monitoring on wearable devices with limited processing capacity. <italic>Methods</italic>: The proposed solution employs a novel architecture consisting of wavelet transform and multiple long short-term memory (LSTM) recurrent neural networks (see <xref ref-type="fig" rid="fig1">Fig. 1</xref>). <italic>Results</italic>: Experimental evaluations show superior ECG classification performance compared to previous works. Measurements on different hardware platforms show the proposed algorithm meets timing requirements for continuous and real-time execution on wearable devices. <italic>Conclusion</italic>: In contrast to many compute-intensive deep-learning based approaches, the proposed algorithm is lightweight, and therefore, brings continuous monitoring with accurate LSTM-based ECG classification to wearable devices. <italic>Significance</italic>: The proposed algorithm is both accurate and lightweight. The source code is available online at <uri>http://lis.ee. sharif.edu</uri>.
Clinical, Pathological, and Genetic Features of Two Chinese Cases with Filamin C Myopathy

To the Editor: Filamin C (FLNC) myopathy is an autosomal dominant inherited myopathy caused by mutations in FLNC. FLNC belongs to the filamin superfamily and cross‐links actin filaments to form a network, anchoring membrane protein to the cytoskeleton. Human protein filamins comprise three isoforms encoded by the human genome: filamins A, B, and C. Among these, FLNC is a Z‐disk protein encoded by the FLNC gene and is mainly expressed in the skeletal and cardiac muscles. FLNC gene is on chromosome 7q32‐q35, containing genomic DNA of about 29.5 kb length and 49 encoding exons. FLNC is an isoform of serine protease expressed primarily in the striated muscle, containing 2725 amino acids, at a molecular weight of 291,000. FLNC protein contains two domains. The amino terminus consists of two calponin homology domains that together constitute the actin‐binding domain (ABD), followed by 24 filamin‐type immunoglobulin (Ig‐FLMN) repeated domains (rod‐overlapping domains), the most carboxy‐terminal of which is responsible for dimerization, assembly, and anchor filaments. Each rod‐overlapping domain consists of seven β‐chains, where 3–4 β‐chains constitute a β‐sheet, and the protein‐binding interface is formed between the two β‐sheets.
Platelet storage properties are associated with donor age: in vitro quality of platelets from young donors and older donors with and without Type 2 diabetes

Previously it has been shown that platelet (PLT) storage performance is consistent by donor. Differences involved metabolic activity, which might be caused by mitochondrial (dys)function, associated with age and age‐related diseases like Type 2 diabetes (T2D). We aimed to test PLTs from young donors in comparison with PLTs from older donors with or without diagnosis for T2D.
Pancreatic Acinar Metaplasia in Distal Esophageal Biopsies Is Associated With Chronic Nonsteroidal Anti-inflammatory Drug Use.

CONTEXT. — The cause of pancreatic acinar metaplasia (PAM) at the distal esophagus/esophagogastric junction is still controversial. Whereas some authors believe it is congenital, others believe it is acquired because of inflammation of the gastric cardia, and more recently it was proposed to be due to chronic proton pump inhibitor use based on a study in rats. OBJECTIVE. — To determine whether there is correlation between chronic proton pump inhibitor use and PAM in humans. We also investigated the correlation between several clinical and pathologic factors and PAM. DESIGN. — Four hundred forty-four consecutive biopsies from the distal esophagus/esophagogastric junction were reviewed for the presence of PAM, which was then correlated with several clinical and pathologic findings. RESULTS. — Pancreatic acinar metaplasia was found in 71 patients (16%). Pancreatic acinar metaplasia was significantly associated with patient age younger than 51 years ( P < .001), chronic carditis ( P = .01), and chronic proton pump inhibitor use ( P = .008). Surprisingly, we also found significant association between PAM and chronic nonsteroidal anti-inflammatory drug use ( P < .001). These associations, including that with chronic nonsteroidal anti-inflammatory drug use, remained significant in multivariate analysis. CONCLUSIONS. — Our findings confirm the previous reports of significant association between PAM and chronic carditis and the findings from animal studies of association with chronic proton pump inhibitor use. The strong association with chronic nonsteroidal anti-inflammatory drug use has not been previously reported and warrants further studies.
An Eye-Tracking Study of Receptive Verb Knowledge in Toddlers.

Purpose We examined receptive verb knowledge in 22- to 24-month-old toddlers with a dynamic video eye-tracking test. The primary goal of the study was to examine the utility of eye-gaze measures that are commonly used to study noun knowledge for studying verb knowledge. Method Forty typically developing toddlers participated. They viewed 2 videos side by side (e.g., girl clapping, same girl stretching) and were asked to find one of them (e.g., "Where is she clapping? "). Their eye-gaze, recorded by a Tobii T60XL eye-tracking system, was analyzed as a measure of their knowledge of the verb meanings. Noun trials were included as controls. We examined correlations between eye-gaze measures and score on the MacArthur-Bates Communicative Development Inventories (CDI; Fenson et al., 1994), a standard parent report measure of expressive vocabulary to see how well various eye-gaze measures predicted CDI score. Results A common measure of knowledge-a 15% increase in looking time to the target video from a baseline phase to the test phase-did correlate with CDI score but operationalized differently for verbs than for nouns. A 2nd common measure, latency of 1st look to the target, correlated with CDI score for nouns, as in previous work, but did not for verbs. A 3rd measure, fixation density, correlated for both nouns and verbs, although the correlation went in different directions. Conclusions The dynamic nature of videos depicting verb knowledge results in differences in eye-gaze as compared to static images depicting nouns. An eye-tracking assessment of verb knowledge is worthwhile to develop. However, the particular dependent measures used may be different than those used for static images and nouns.
Changing demographics of scientific careers: The rise of the temporary workforce

Contemporary science has been characterized by an exponential growth in publications and a rise of team science. At the same time, there has been an increase in the number of awarded PhD degrees, which has not been accompanied by a similar expansion in the number of academic positions. In such a competitive environment, an important measure of academic success is the ability to maintain a long active career in science. In this paper, we study workforce trends in three scientific disciplines over half a century. We find dramatic shortening of careers of scientists across all three disciplines. The time over which half of the cohort has left the field has shortened from 35 y in the 1960s to only 5 y in the 2010s. In addition, we find a rapid rise (from 25 to 60% since the 1960s) of a group of scientists who spend their entire career only as supporting authors without having led a publication. Altogether, the fraction of entering researchers who achieve full careers has diminished, while the class of temporary scientists has escalated. We provide an interpretation of our empirical results in terms of a survival model from which we infer potential factors of success in scientific career survivability. Cohort attrition can be successfully modeled by a relatively simple hazard probability function. Although we find statistically significant trends between survivability and an author’s early productivity, neither productivity nor the citation impact of early work or the level of initial collaboration can serve as a reliable predictor of ultimate survivability.
Encounters From Device Complications Among Children With Medical Complexity.

OBJECTIVES Children with medical complexity (CMC) are commonly assisted by medical devices to support essential body functions, although complications may lead to preventable emergency department (ED) and hospital use. Our objective was to identify predictors of device-complicated ED visits and hospitalizations. METHODS This single-center retrospective cohort study included patients referred to a Pediatric Complex Care Program between April 1, 2014, and April 30, 2016, assisted by at least 1 medical device. Hospitalizations and ED visits in the year before enrollment were rated for likelihood for being due to device complications. Interrater reliability among 3 independent reviewers was assessed. Bivariate followed by multivariate logistic regression clustered by patient helped us identify associations between demographic, clinical, and device characteristics associated with device-complicated ED or hospital encounters. RESULTS Interrater reliability was high (κ = 0.92). Among 98 CMC, device-complicated encounters represented 17% of 258 hospitalizations and 31% of 228 ED visits. Complications of 3 devices (central venous catheters, enteral tubes, and tracheostomy tubes) accounted for 13% of overall hospitalizations and 28% of overall ED visits. Central venous catheter presence (adjusted odds ratio [aOR] 3.2 [95% confidence interval (CI) 1.1-9.5]) was associated with device-complicated ED visits. Gastrojejunostomy/jejunostomy tube presence (aOR 3.3 [95% CI 1.5-7.5]) or tracheostomies with (aOR 8.1 [95% CI 2.3-28.5]) or without (aOR 4.5 [95% CI 1.7-7.5]) ventilator use was associated with device-complicated hospitalizations. Clinical variables were poor predictors of device-complicated encounters. CONCLUSIONS Device-complicated ED visits and hospitalizations comprised a substantial proportion of total hospital and ED use. Developing interventions to prevent device complications may be a promising strategy to reduce overall CMC use.
Meta-Narrative Review of Molecular Methods for Diagnosis and Monitoring of Multidrug-Resistant Tuberculosis Treatment in Adults

Early and accurate diagnosis and rigorous clinical and microbiological monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment can curb morbidity and mortality. While others are still under evaluation, the World Health Organization has recommended few novel molecular methods for MDR-TB diagnosis only. We present current molecular methods for diagnosis and monitoring of MDR-TB treatment in TB-endemic settings. A systematic meta-narrative review was conducted according to the RAMESES recommendations. Electronic databases were searched for relevant articles published in English language from January 2013 to June 2018. Based on predefined criteria, two independent reviewers extracted the key messages from relevant articles. Disagreement between them was resolved through discussion and the involvement of a third reviewer, if needed. Key messages were synthesized to create the meta-narratives for method's accuracy, drug-susceptibility capability, and laboratory infrastructure required. We included 33 articles out of 1213 records retrieved, of which 16 (48%) and 12 (36%) were conducted in high- and low-TB-endemic settings, respectively. Xpert® MTB/RIF, GenoType MTBDRplus, GenoType MTBDRsl, FlouroType™ MTBDR, TB TaqMan® array card, and DNA sequencers can accurately guide effective treatment regimens. Molecular bacterial load assay quantifies mycobactericidal impact of these regimens. Although they present inherent advantages compared to the current standard of care, they carry important limitations to implementation and/or scale-up. Therefore, considerable effort must now be directed to implementation and health systems research to maximize these forecasted benefits for individual patient's health outcomes.
Disruption of the default mode network and its intrinsic functional connectivity underlies minor hallucinations in Parkinson's disease

Minor hallucinations and well‐structured hallucinations are considered in the severity continuum of the psychotic spectrum associated with Parkinson's disease. Although their chronological relationship is largely unknown, the spatial patterns of brain atrophy in these 2 forms of hallucinations partially overlap, suggesting they share similar pathophysiological processes. Functional connectivity studies show that disruption of functional networks involved in perception and attention could be relevant in the emergence of well‐structured hallucinations. However, functional neuroimaging studies in patients with isolated minor hallucinations are lacking. The objectives of this study were to explore the structural and functional changes underlying minor hallucinations.
The 40S ribosomal protein uS5 (RPS2) assembles into an extraribosomal complex with human ZNF277 that competes with the PRMT3–uS5 interaction

Ribosomal (r)-proteins are generally viewed as ubiquitous, constitutive proteins that simply function to maintain ribosome integrity. However, findings in the past decade have led to the idea that r-proteins have evolved specialized functions beyond the ribosome. For example, the 40S ribosomal protein uS5 (RPS2) is known to form an extraribosomal complex with the protein arginine methyltransferase PRMT3 that is conserved from fission yeast to humans. However, the full scope of uS5's extraribosomal functions, including whether uS5 interacts with any other proteins, is not known. In this study, we identify the conserved zinc finger protein 277 (ZNF277) as a new uS5-associated protein by using quantitative proteomics approaches in human cells. As previously shown for PRMT3, we found that ZNF277 uses a C2H2-type zinc finger domain to recognize uS5. Analysis of protein–protein interactions in living cells indicated that the ZNF277–uS5 complex is found in the cytoplasm and the nucleolus. Furthermore, we show that ZNF277 and PRMT3 compete for uS5 binding, because overexpression of PRMT3 inhibited the formation of the ZNF277–uS5 complex, whereas depletion of cellular ZNF277 resulted in increased levels of uS5-PRMT3. Notably, our results reveal that ZNF277 recognizes nascent uS5 in the course of mRNA translation, suggesting cotranslational assembly of the ZNF277–uS5 complex. Our findings thus unveil an intricate network of evolutionarily conserved protein–protein interactions involving extraribosomal uS5, suggesting a key role for uS5 beyond the ribosome.