Miracle-dz/UniFAR-FTUs huggingface dataset:
Prenatal Selective Serotonin Reuptake Inhibitor Use and Associated Risk for Gestational Hypertension and Preeclampsia: A Meta-Analysis of Cohort Studies.

BACKGROUND To analyze existing cohort studies and provide evidence for the use of prenatal selective serotonin reuptake inhibitor (SSRI) monotherapy and the associated risk of gestational hypertension and preeclampsia. METHODS A comprehensive search of English language articles published before 30th April 2017 was conducted on PubMed, EMBASE, and the Web of Science databases. Using data acquired, we summarized the relative risks (RRs) and 95% confidence intervals (CIs) of gestational hypertension and preeclampsia using the random-effects model. Heterogeneity between studies was also assessed with the I2 statistic. RESULTS Seven cohort studies with 1,108,261 individuals were included for analysis. Compared with nonusers, those undertaking prenatal SSRI monotherapy were more likely to develop gestational hypertension or preeclampsia (summarized RR = 1.21, 95% CI: 1.05-1.40, I2 = 71.3%), gestational hypertension (summarized RR = 1.14, 95% CI: 1.00-1.30, I2 = 5.7%), and preeclampsia (summarized RR = 1.32, 95% CI: 0.99-1.78, I2 = 83.3%). In addition, although subgroup analyses, which were stratified by study design, number of cases, geographic location, duration of SSRI monotherapy, registry databases, and adjustment for potential confounders and risk factors, were consistent with the main findings, not all of these showed statistical significance. No evidence of publication bias was detected. CONCLUSIONS Women who receive SSRI monotherapy during pregnancy are at increased risk of gestational hypertension and preeclampsia.
Heart failure drug changes the mechanoenzymology of the cardiac myosin powerstroke

Significance Heart failure is the leading cause of mortality in the United States, despite sustained efforts to develop effective small-molecule treatments. The biophysical characterization of existing therapies will drive development of next-generation approaches for treating heart failure. Furthermore, small molecules can be powerful probes for dissecting protein structure function relationships. We used an innovative FRET-based spectroscopic approach to determine that the small-molecule heart disease therapeutic omecamtiv mecarbil (OM) changes how myosin’s working powerstroke is coordinated with actin-activated phosphate release, the biochemical step associated with force generation. This result explains how OM alters cardiac contractility at the molecular level, forcing the accumulation of actin-bound prepowerstroke cross-bridges. Omecamtiv mecarbil (OM), a putative heart failure therapeutic, increases cardiac contractility. We hypothesize that it does this by changing the structural kinetics of the myosin powerstroke. We tested this directly by performing transient time-resolved FRET on a ventricular cardiac myosin biosensor. Our results demonstrate that OM stabilizes myosin’s prepowerstroke structural state, supporting previous measurements showing that the drug shifts the equilibrium constant for myosin-catalyzed ATP hydrolysis toward the posthydrolysis biochemical state. OM slowed the actin-induced powerstroke, despite a twofold increase in the rate constant for actin-activated phosphate release, the biochemical step in myosin’s ATPase cycle associated with force generation and the conversion of chemical energy into mechanical work. We conclude that OM alters the energetics of cardiac myosin’s mechanical cycle, causing the powerstroke to occur after myosin weakly binds to actin and releases phosphate. We discuss the physiological implications for these changes.
High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact.
Drug Use Status in Youth: The Role of Gender and Delay Discounting

ABSTRACT Background: Evidence from gender and delay discounting studies suggests these variables may influence drug use in youth. However, no studies to date have examined sexual discounting with regard to drug use in youth. Objectives: The present study examined gender and delay discounting, both monetary and sexual, with regard to the drug use status of alcohol, tobacco, and marijuana. Methods: Youth aged 14–21 years (n = 155) provided demographic and drug use information and completed behavioral tasks assessing monetary and sexual discounting in a single laboratory session. Chi-square and analysis of variance were used to assess group differences. Results: Across drug use status, differences in gender and sexual discounting but not monetary discounting were found. Moderate drinkers and smokers were more likely to be male and displayed steeper sexual discounting rates. However, no interaction effect between gender and discounting differences on drug use status was observed. Conclusions: Findings suggest that drug use may manifest differently by gender and highlight the domain specificity of sexual discounting. These findings further highlight the need to incorporate gender and domain-specific discounting measures when investigating drug use pathology and interventions in youth.
Misuse of Pediatric Medications and Parent-Physician Communication: An Interactive Voice Response Intervention.

BACKGROUND Children take 1 medication each week on average at home. Better communication between parents and providers could support safer home medication use and prevent misuse of pediatric medications, such as intentional underdosing or overdosing. Our primary objective was to assess the impact of an interactive voice response system on parent-provider communication about medications. METHODS Parents of children 4 months to 11 years of age with upcoming well child visits were invited to call our interactive voice response system, called Personal Health Partner (PHP), which asked questions about the child's health and medication use. Responding parents were randomized to either PHP (interview and counseling) or control (injury prevention survey). Parents' responses were embedded in the electronic health record. After the physical visit, research assistants performed a phone follow-up survey. RESULTS Of 475 parents, including 293 PHPs and 182 controls, 93% were women. We found a high prevalence of misuse of medications: 14% reported underdosing (n = 63) fever-reducer medications and 3% reported overdosing (n = 13). Twenty percent (n = 37) of the 190 children younger than 3 years had received cold medication. Thirty-three percent (n = 19) of 62 PHP parents of children on prescription medications reported nonadherence. Among children on prescription medications, PHP significantly increased discussion of medications at the physical, but not the number who brought medications to the visit; it had no impact on those not on prescription medications. CONCLUSIONS Pediatric medication misuse was common in this study. Use of a previsit interactive voice response system increased medication-related communication during visits and supports the need for systems that better prepare patients for visits and improve medication-related patient-physician communication.
Fatigue limit in borosilicate glass by interrupted static fatigue test

The threshold stress intensity factor, K th , for sub-critical crack growth of borosilicate glass was measured in water environment using the interrupted static fatigue test. Bending tests with durations ranging from 1 h to 50 days were performed. Around 15 specimens were tested at each condition and the constant stress applied varied from 70 to 95 MPa, The stress intensity factor, K w , applied to the weakest surviving sample during the stress hold was calculated as a function of the dwell time. K w was seen to decrease with the hold time until an invariant stress intensity factor corresponding to the fatigue limit (K th 0.26-0.29 M Pa√m) was reached for durations larger than 10 days.
Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

ABSTRACT Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1−/− mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1−/− mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b+ macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice.
Preeminent risk factor affecting software development

Software project management has a significant focus on software risk management. The major objective of this study is to identify, analyze and list out the principal vital risk factors within the life cycle of a project. This paper, presents a comprehensive analysis on risk factors that can possibly occur during each phase of SDLC. The risk factors are endorsed by using questionnaires conducted from the employees and employers of various software companies, which handle the day to day challenges efficiently. After collecting data from the pilot study and questionnaires a statistical analysis is performed using SPSS (Statistical package for the social science) to predict the risk impact on cost. The inquisitive analysis can help to develop and foretell the strategies for assessment, control and reduction of the risk factors which will enable to make suitable decisions regarding project success.
The Influence of E1A C-Terminus on Adenovirus Replicative Cycle

Adenovirus Early 1A proteins (E1A) are crucial for initiation of the viral life cycle after infection. The E1A gene is encoded at the left end of the viral genome and consists of two exons, the first encoding 185 amino acids in the 289 residues adenovirus 5 E1A, while the second exon encodes 104 residues. The second exon-encoded region of E1A is conserved across all E1A isoforms except for the 55 residues protein, which has a unique C-terminus due to a frame shift following splicing into the second exon. This region of E1A contributes to a variety of processes including the regulation of viral and cellular gene expression, immortalization and transformation. Here we evaluated the contributions that different regions of the second exon of E1A make to the viral life cycle using deletion mutants. The region of E1A encoded by the second exon was found to be important for overall virus growth, induction of viral and cellular gene expression, viral genome replication and deregulation of the cell cycle. Efficient viral replication was found to require exon 2 and the nuclear localization signal, as loss of either resulted in severe growth deficiency. Induction of cellular DNA synthesis was also deficient with any deletion of E1A within the C-terminus even if these deletions were outside of conserved region 4. Overall, our study provides the first comprehensive insight into the contributions of the C-terminus of E1A to the replicative fitness of human adenovirus 5 in arrested lung fibroblasts.
A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients

Purpose: Hypoxia modification improves overall survival in muscle-invasive bladder cancer patients who undergo radiotherapy. There is evidence that hypoxic tumors benefit most from hypoxia modification. The study aimed to identify or derive a hypoxia gene signature that predicts benefit from hypoxia-modifying treatment in bladder cancer. Experimental Design: Published hypoxia signatures were tested and a new one derived by analyzing bladder cancer transcriptomic data from public databases. Tumor samples were available from the BCON phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Gene expression data were generated for 151 tumors using Affymetrix Human 1.0 Exon ST arrays and used for independent validation. Results: A 24-gene signature was derived, which was prognostic in four of six independent surgical cohorts (n = 679; meta HR, 2.32; 95% CI, 1.73–3.12; P < 0.0001). The signature was also prognostic in BCON patients receiving radiotherapy alone (n = 75; HR for local relapse-free survival, 2.37; 95% CI, 1.26–4.47; P = 0.0076). The signature predicted benefit from CON (n = 76; HR, 0.47; 95% CI, 0.26–0.86; P = 0.015). Prognostic significance (P = 0.017) and predictive significance (P = 0.058) remained after adjusting for clinicopathologic variables. A test for interaction between hypoxia status and treatment arms was significant (P = 0.0094). Conclusions: A 24-gene hypoxia signature has strong and independent prognostic and predictive value for muscle-invasive bladder cancer patients. The signature can aid identification of patients likely to benefit from the addition of carbogen and nicotinamide to radiotherapy. Clin Cancer Res; 23(16); 4761–8. ©2017 AACR.
Encoding model of temporal processing in human visual cortex

Significance How is temporal information processed in human visual cortex? To address this question, we used fMRI and a two temporal channel-encoding model. This approach not only explains cortical responses for time-varying stimuli ranging from milliseconds to seconds but finds differential temporal processing across human visual cortex. While motion-sensitive regions are dominated by transient responses, ventral regions that process the content of the visual input surprisingly show both sustained and transient responses, with the latter exceeding the former. This transient processing may foster rapid extraction of the gist of the scene. Importantly, our encoding approach marks a transformative advancement in the temporal resolution of fMRI, as it enables linking fMRI responses to the timescale of neural computations in cortex. How is temporal information processed in human visual cortex? Visual input is relayed to V1 through segregated transient and sustained channels in the retina and lateral geniculate nucleus (LGN). However, there is intense debate as to how sustained and transient temporal channels contribute to visual processing beyond V1. The prevailing view associates transient processing predominately with motion-sensitive regions and sustained processing with ventral stream regions, while the opposing view suggests that both temporal channels contribute to neural processing beyond V1. Using fMRI, we measured cortical responses to time-varying stimuli and then implemented a two temporal channel-encoding model to evaluate the contributions of each channel. Different from the general linear model of fMRI that predicts responses directly from the stimulus, the encoding approach first models neural responses to the stimulus from which fMRI responses are derived. This encoding approach not only predicts cortical responses to time-varying stimuli from milliseconds to seconds but also, reveals differential contributions of temporal channels across visual cortex. Consistent with the prevailing view, motion-sensitive regions and adjacent lateral occipitotemporal regions are dominated by transient responses. However, ventral occipitotemporal regions are driven by both sustained and transient channels, with transient responses exceeding the sustained. These findings propose a rethinking of temporal processing in the ventral stream and suggest that transient processing may contribute to rapid extraction of the content of the visual input. Importantly, our encoding approach has vast implications, because it can be applied with fMRI to decipher neural computations in millisecond resolution in any part of the brain.
Treating depression with physical activity in adolescents and young adults: a systematic review and meta-analysis of randomised controlled trials

Abstract We aimed to establish the treatment effect of physical activity for depression in young people through meta-analysis. Four databases were searched to September 2016 for randomised controlled trials of physical activity interventions for adolescents and young adults, 12–25 years, experiencing a diagnosis or threshold symptoms of depression. Random-effects meta-analysis was used to estimate the standardised mean difference (SMD) between physical activity and control conditions. Subgroup analysis and meta-regression investigated potential treatment effect modifiers. Acceptability was estimated using dropout. Trials were assessed against risk of bias domains and overall quality of evidence was assessed using GRADE criteria. Seventeen trials were eligible and 16 provided data from 771 participants showing a large effect of physical activity on depression symptoms compared to controls (SMD = −0.82, 95% CI = −1.02 to −0.61, p < 0.05, I2 = 38%). The effect remained robust in trials with clinical samples (k = 5, SMD = −0.72, 95% CI = −1.15 to −0.30), and in trials using attention/activity placebo controls (k = 7, SMD = −0.82, 95% CI = −1.05 to −0.59). Dropout was 11% across physical activity arms and equivalent in controls (k = 12, RD = −0.01, 95% CI = −0.04 to 0.03, p = 0.70). However, the quality of RCT-level evidence contributing to the primary analysis was downgraded two levels to LOW (trial-level risk of bias, suspected publication bias), suggesting uncertainty in the size of effect and caution in its interpretation. While physical activity appears to be a promising and acceptable intervention for adolescents and young adults experiencing depression, robust clinical effectiveness trials that minimise risk of bias are required to increase confidence in the current finding. The specific intervention characteristics required to improve depression remain unclear, however best candidates given current evidence may include, but are not limited to, supervised, aerobic-based activity of moderate-to-vigorous intensity, engaged in multiple times per week over eight or more weeks. Further research is needed. (Registration: PROSPERO-CRD 42015024388).
Automatic Counting of Wheat Spikes from Wheat Growth Images

This study aims to develop an automated screening system that can estimate the number of wheat spikes (i.e. ears) from a given wheat plant image acquired after the flowering stage. The platform can be used to assist the dynamic estimation of wheat yield potential as well as grain yield based on wheat images captured by the CropQuant platform. Our proposed system framework comprises three main stages. Firstly, it transforms the wheat plant raw image data using colour index of vegetation extraction (CIVE) and then segments wheat ear regions from the image to reduce the influence of the background signals. Secondly, it detects wheat ears using Gabor filter banks and K-means clustering algorithm. Finally, it estimates the number of wheat spikes within extracted wheat spike region through a regression method. The framework is tested with a real-world dataset of wheat growth images equally distributed from flowering to ripening stages. The estimations of the wheat ears were benchmarked against the ground truth produced in this study by human manual counting. Our automatic counting system achieved an average accuracy of 90.7% with a standard deviation of 0.055, at a much faster speed than human experts and hence the system has a potential to be improved for agricultural applications on wheat growth studies in the future.
Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study

ABSTRACT Neurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.