Miracle-dz/UniFAR-FTUs huggingface dataset:
Prenatal exposure to fever is associated with autism spectrum disorder in the boston birth cohort

Autism spectrum disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under‐represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR 2.02 [1.04–3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age, and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00–7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Autism Res 2017, 10: 1878–1890. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Incidence and follow‐up of patients with focal prostate carcinoma in 2 screening rounds after an interval of 4 years

Focal carcinoma detected by needle biopsy has been a common finding since prostate‐specific antigen (PSA)‐based screening was introduced. Clinicopathologic features in patients with focal prostate carcinoma who underwent radical prostatectomy (RP) or who were treated with watchful waiting (WW) were analyzed to detect clinical predictors for disease progression during follow‐up.
Effects of a moderate evening alcohol dose. I: sleepiness.

BACKGROUND Few studies examining alcohol's effects consider prior sleep/wake history and circadian timing. We examined introspective and physiological sleepiness on nights with and without moderate alcohol consumption in well-rested young adults at a known circadian phase. METHODS Twenty-nine adults (males=9), ages 21 to 25 years (M=22.6, SD=1.2), spent 1 week on an at-home stabilized sleep schedule (8.5 or 9 hours), followed by 3 in-lab nights: adaptation, placebo, and alcohol. Alcohol (vodka; 0.54 g/kg for men; 0.49 g/kg for women) or placebo beverage was consumed over 30 minutes ending 1 hour before stabilized bedtime. In addition to baseline, 3 sleep latency tests (SLTs) occurred after alcohol/placebo ingestion (15, 16.5, and 18 hours after waking). Stanford Sleepiness Scales (SSS) and Visual Analog Scales (VAS) of sleepiness were completed before each SLT and approximately every 30 minutes. The Biphasic Alcohol Effects Scale (BAES) was administered a total of 4 times (baseline, 5, 60, and 90 minutes postalcohol/placebo). Subjects' circadian phase was determined from melatonin levels in saliva samples taken at approximately 30-minute intervals. RESULTS All sleepiness and sedation measures increased with time awake. Only SSS and BAES sedation measures showed higher levels of sleepiness and sedation after alcohol compared with placebo. The mean circadian phase was the same for assessments at both conditions. CONCLUSIONS Alcohol did not increase physiological sleepiness compared with placebo nor was residual sedation evident under these conditions. We conclude that the effects on sleepiness of a moderate dose of alcohol are masked when sleep-wake homeostatic and circadian timing influences promote high levels of sleepiness.
The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1

In the present study, we addressed the role of the c-jun proto-oncogene in the mitogenic response of human fibroblasts and primary acute myelogenous leukemia blasts to tumor necrosis factor alpha (TNF-alpha). Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun, resulting in accumulation of c-jun mRNA and protein expression. In order to elucidate the role of c-Jun/AP-1 in TNF-mediated growth stimulation, the antisense (AS) technique was used. Uptake studies of oligonucleotides were performed with fibroblasts, demonstrating that incorporation of oligomers was maximal at 4 h. Oligodeoxynucleotides remained stable in these cells for up to 24 h. Treatment of fibroblasts with the AS oligonucleotide resulted in intracellular duplex formation followed by an efficient translation blockade of c-Jun/AP-1. In contrast, sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c-Jun/AP-1, suggesting specific elimination of c-Jun/AP-1 by the AS oligomer. Fibroblasts cultured in the presence of the AS oligonucleotide but not those cultured in the presence of the S or NS oligonucleotide failed to respond proliferatively to TNF-alpha. These findings could be confirmed by experiments with primary acute myelogenous leukemia blasts, which also demonstrated that TNF-induced growth stimulation required c-Jun/AP-1 function. Taken together, our results indicate that activation of c-Jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF, which leads to a proliferative response of its target cells.
Patient Satisfaction as a Predictor of Return‐to‐Provider Behavior: Analysis and Assessment of Financial Implications

Although customer loyalty is frequently cited as a benefit of patient satisfaction, an empirical link between the two has not, to our knowledge, ever been statistically established in a hospital setting. The goal of the present study was to evaluate the relationship between self-reported patient satisfaction measures and subsequent return to the provider for care at a large academic medical center. Data from all adult medical patients responding to a patient satisfaction survey distributed by a large midwestern academic medical center during fiscal year 1997 (n = 1485) were analyzed. Response patterns were examined as they related to whether patients returned to the provider during the subsequent 2-year period. Analyses suggested that return-to-provider was associated with only a minority of the satisfaction items (approx. 11%). All items showing a significant relationship measured perceptions of how well physicians and nurses attended to, and provided information to, patients and their families. Although the size of these relationships was generally small, the estimated financial implications are substantial. Other implications of these findings for planning effective service improvement initiatives as well as improving patient survey design are discussed.
Characterizing Verified Head Impacts in High School Girls’ Lacrosse

Background: Girls’ high school lacrosse players have higher rates of head and facial injuries than boys. Research indicates that these injuries are caused by stick, player, and ball contacts. Yet, no studies have characterized head impacts in girls’ high school lacrosse. Purpose: To characterize girls’ high school lacrosse game-related impacts by frequency, magnitude, mechanism, player position, and game situation. Study Design: Descriptive epidemiology study. Methods: Thirty-five female participants (mean age, 16.2 ± 1.2 years; mean height, 1.66 ± 0.05 m; mean weight, 61.2 ± 6.4 kg) volunteered during 28 games in the 2014 and 2015 lacrosse seasons. Participants wore impact sensors affixed to the right mastoid process before each game. All game-related impacts recorded by the sensors were verified using game video. Data were summarized for all verified impacts in terms of frequency, peak linear acceleration (PLA), and peak rotational acceleration (PRA). Descriptive statistics and impact rates were calculated. Results: Fifty-eight verified game-related impacts ≥20g were recorded (median PLA, 33.8g; median PRA, 6151.1 rad/s2) during 467 player-games. The impact rate for all game-related verified impacts was 0.12 per athlete-exposure (AE) (95% CI, 0.09-0.16), equivalent to 2.1 impacts per team game, indicating that each athlete suffered fewer than 2 head impacts per season ≥20g. Of these impacts, 28 (48.3%) were confirmed to directly strike the head, corresponding with an impact rate of 0.05 per AE (95% CI, 0.00-0.10). Overall, midfielders (n = 28, 48.3%) sustained the most impacts, followed by defenders (n = 12, 20.7%), attackers (n = 11, 19.0%), and goalies (n = 7, 12.1%). Goalies demonstrated the highest median PLA and PRA (38.8g and 8535.0 rad/s2, respectively). The most common impact mechanisms were contact with a stick (n = 25, 43.1%) and a player (n = 17, 29.3%), followed by the ball (n = 7, 12.1%) and the ground (n = 7, 12.1%). One hundred percent of ball impacts occurred to goalies. Most impacts occurred to field players within the attack area of the field (n = 32, 55.2%) or the midfield (n = 18, 31.0%). Most (95%) impacts did not result in a penalty. Conclusion: The incidence of verified head impacts in girls’ high school lacrosse was quite low. Ball to head impacts were associated with the highest impact magnitudes. While stick and body contacts are illegal in girls’ high school lacrosse, rarely did such impacts to the head result in a penalty. The verification of impact mechanisms using video review is critical to collect impact sensor data.
Loss of tumour suppressor PTEN expression in renal injury initiates SMAD3‐ and p53‐dependent fibrotic responses

Deregulation of the tumour suppressor PTEN occurs in lung and skin fibrosis and diabetic and ischaemic renal injury. However, the potential role of PTEN and associated mechanisms in the progression of kidney fibrosis is unknown. Tubular and interstitial PTEN expression was dramatically decreased in several models of renal injury, including aristolochic acid nephropathy (AAN), streptozotocin (STZ)‐mediated injury and ureteral unilateral obstruction (UUO), correlating with Akt, p53 and SMAD3 activation and fibrosis. Stable silencing of PTEN in HK‐2 human tubular epithelial cells induced dedifferentiation and CTGF, PAI‐1, vimentin, α‐SMA and fibronectin expression, compared to HK‐2 cells expressing control shRNA. Furthermore, PTEN knockdown stimulated Akt, SMAD3 and p53Ser15 phosphorylation, with an accompanying decrease in population density and an increase in epithelial G1 cell cycle arrest. SMAD3 or p53 gene silencing or pharmacological blockade partially suppressed fibrotic gene expression and relieved growth inhibition orchestrated by deficiency or inhibition of PTEN. Similarly, shRNA suppression of PAI‐1 rescued the PTEN loss‐associated epithelial proliferative arrest. Moreover, TGFβ1‐initiated fibrotic gene expression is further enhanced by PTEN depletion. Combined TGFβ1 treatment and PTEN silencing potentiated epithelial cell death via p53‐dependent pathways. Thus, PTEN loss initiates tubular dysfunction via SMAD3‐ and p53‐mediated fibrotic gene induction, with accompanying PAI‐1‐dependent proliferative arrest, and cooperates with TGFβ1 to induce the expression of profibrotic genes and tubular apoptosis. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
[Expression of CD147 and MMP-2 in human gliomas and its correlations with prognosis].

OBJECTIVE To investigate the expressions of CD147 and MMP-2 in human gliomas and to study the relationship between their expression and prognosis. METHODS Immunohistochemistry SP methods were applied to detect the expression of CD147 and MMP-2 in 50 cases of gliomas and RT-PCR also applied to analyze the expression level of CD147 mRNA. The relationship between the expression level and the glioma prognosis were analyzed statistically depends on the follow-up investigation of the disease development. RESULTS The positive rates of CD147 and MMP-2 in human gliomas were 72. 0% and 78. 0%, and coexpression of CD147 and MMP-2 in gliomas was 70. 0%. CD147 protein was positively correlated with the expression of MMP-2 protein (r =0. 737, P<0. 01). CD147 mRNA expression was also detected in low and high grade gliomas by RT-PCR, but their expression levels were obviously enhanced in high grade gliomas. There was a significant difference in each grade gliomas. The higher expression of CD147, the shorter survival time of the patients. The variations were significant statistically. CONCLUSION There was positive correlation between the expressions of CD147, MMP-2 in human gliomas and the degree of malignancy and prognosis. CD147 and MMP-2 may be a prognostic factor of human gliomas and targets for chemotherapeutical strategies.
Schizophrenic subjects with no history of admission to hospital

SYNOPSIS It has often been assumed that all subjects with schizophrenia will eventually be admitted to hospital and therefore little bias is introduced by restricting research to hospitalized subjects. Using the Lothian Psychiatric Case Register, 66 subjects were identified who had been diagnosed in Edinburgh as suffering from schizophrenia between 1978 and 1989 but had no history of hospital admission by December 1991. This represented an adjusted average of 6·7% of the estimated annual rate of first diagnosis of schizophrenia: the proportion of such patients did not change over the period. Using a case–control design, the index cases were compared with a control group of schizophrenic patients who had been admitted to hospital within 3 months of diagnosis. At the time of diagnosis, the cases were generally less disturbed with lower levels of violent behaviour and less evidence of neglect or hallucinations. They had a longer duration of illness prior to diagnosis, were more often diagnosed by a consultant and unemployed. In a follow-up study of the index cases, 59 (89%) were traced, of whom 6 (10%) were deceased. The outcome of the illness was heterogeneous although the course was often chronic. The general practitioner provided most of the care they received. The small proportion of such patients suggests that their exclusion from most published series does not seriously bias our picture of the natural history of schizophrenia. Moreover, as there was no increase in the proportion over the period, first admission rates for schizophrenia in Scotland are a reasonable approximation to incidence rates.
Suitability of point kernel dose calculation techniques in brachytherapy treatment planning

Brachytherapy treatment planning system (TPS) is necessary to estimate the dose to target volume and organ at risk (OAR). TPS is always recommended to account for the effect of tissue, applicator and shielding material heterogeneities exist in applicators. However, most brachytherapy TPS software packages estimate the absorbed dose at a point, taking care of only the contributions of individual sources and the source distribution, neglecting the dose perturbations arising from the applicator design and construction. There are some degrees of uncertainties in dose rate estimations under realistic clinical conditions. In this regard, an attempt is made to explore the suitability of point kernels for brachytherapy dose rate calculations and develop new interactive brachytherapy package, named as BrachyTPS, to suit the clinical conditions. BrachyTPS is an interactive point kernel code package developed to perform independent dose rate calculations by taking into account the effect of these heterogeneities, using two regions build up factors, proposed by Kalos. The primary aim of this study is to validate the developed point kernel code package integrated with treatment planning computational systems against the Monte Carlo (MC) results. In the present work, three brachytherapy applicators commonly used in the treatment of uterine cervical carcinoma, namely (i) Board of Radiation Isotope and Technology (BRIT) low dose rate (LDR) applicator and (ii) Fletcher Green type LDR applicator (iii) Fletcher Williamson high dose rate (HDR) applicator, are studied to test the accuracy of the software. Dose rates computed using the developed code are compared with the relevant results of the MC simulations. Further, attempts are also made to study the dose rate distribution around the commercially available shielded vaginal applicator set (Nucletron). The percentage deviations of BrachyTPS computed dose rate values from the MC results are observed to be within plus/minus 5.5% for BRIT LDR applicator, found to vary from 2.6 to 5.1% for Fletcher green type LDR applicator and are up to −4.7% for Fletcher-Williamson HDR applicator. The isodose distribution plots also show good agreements with the results of previous literatures. The isodose distributions around the shielded vaginal cylinder computed using BrachyTPS code show better agreement (less than two per cent deviation) with MC results in the unshielded region compared to shielded region, where the deviations are observed up to five per cent. The present study implies that the accurate and fast validation of complicated treatment planning calculations is possible with the point kernel code package.
Comparison of the EF-1 alpha and the CMV promoter for engineering stable tumor cell lines using recombinant adeno-associated virus.

BACKGROUND Silencing of the viral CMV immediate early enhancer promoter can be a problem in certain cell types when engineering stable cell lines. MATERIALS AND METHODS We compared the efficacy of the CMV promoter to the promoter of the elongation factor-1 alpha (EF-1 alpha) for the generation of stable colon carcinoma cell lines (HT-29). Green fluorescent protein (GFP) expression cassettes were delivered by recombinant adeno-associated virus (AAV) which is known for its ability to stably transduce cells. Stable cell lines were characterized in vitro by FACS and in vivo after HT-29 clones were grown as xenografts in nude mice. RESULTS Stable HT-29 clones with > 97% of all cells homogeneously expressing GFP were generated with the EF-1 alpha promoter. In contrast in clones carrying the CMV promoter, only up to 60% of the cells were GFP-positive with expression levels varying widely between cells. Superinfection with wild-type adenovirus induced GFP expression in more than 90% of the cells indicating that the CMV promoter was silenced. In vivo the tumors carrying the EF-1 alpha promoter were homogeneously GFP-positive, whereas the CMV promoter gave rise to a scattered pattern of GFP expression. CONCLUSION This study underlines the importance of the promoter for the generation of stable cell lines. In addition it demonstrates that recombinant AAV can effectively be used as a gene delivery system for this purpose.
Abundance and distribution of the highly iterated palindrome 1 (HIP1) among prokaryotes

We have studied the abundance and phylogenetic distribution of the Highly Iterated Palindrome 1 (HIP1) among sequenced prokaryotic genomes. We show that an overrepresentation of HIP1 is exclusive of some lineages of cyanobacteria, and that this abundance was gained only once during evolution and was subsequently lost in the lineage leading to marine pico-cyanobacteria. We show that among cyanobacterial protein sequences with annotated Pfam domains, only OpcA (glucose 6-phosphate dehydrogenase assembly protein) has a phylogenetic distribution fully matching HIP1 abundance, suggesting a functional relationship; we also show that DAM methylase (an enzyme that has the four central nucleotides of HIP1 as is site of action) is present in all cyanobacterial genomes (independently of their HIP1 content) with the exception of marine pico-cyanobacteria whom might have lost this enzyme during the process of genome reduction. Our analyses also show that in some prokaryotic lineages (particularly in those species with large genomes), HIP1 is unevenly distributed between coding and non-coding DNA (being more common in coding regions; with the exception of Cyanobacteria Yellowstone B’ and Synechococcus elongates where the reverse pattern is true). Finally, we explore the hypothesis that the HIP1 can be used as a molecular “water-mark” to identify horizontally transferred genes from cyanobacteria to other species.
Molecular Properties of Zic Proteins as Transcriptional Regulators and Their Relationship to GLI Proteins*

Zic family genes encode zinc finger proteins, which play important roles in vertebrate development. The zinc finger domains are highly conserved between Zic proteins and show a notable homology to those of Gli family proteins. In this study, we investigated the functional properties of Zic proteins and their relationship to the GLI proteins. We first established an optimal binding sequence for Zic1, Zic2, and Zic3 proteins by electrophoretic mobility shift assay-based target selection and mutational analysis. The selected sequence was almost identical to the GLI binding sequence. However, the binding affinity was lower than that of GLI. Consistent results were obtained in reporter assays, in which transcriptional activation by Zic proteins was less dependent on the GLI binding sequence than GLI1. Moreover, Zic proteins activated a wide range of promoters irrespective of the presence of a GLI binding sequence. When Zic and GLI proteins were cotransfected into cultured cells, Zic proteins enhanced or suppressed sequence-dependent, GLI-mediated transactivation depending on cell type. Taken together, these results suggest that Zic proteins may act as transcriptional coactivators and that their function may be modulated by the GLI proteins and possibly by other cell type-specific cofactors.
Caspase Activation and Specific Cleavage of Substrates after Coxsackievirus B3-Induced Cytopathic Effect in HeLa Cells

ABSTRACT Coxsackievirus B3 (CVB3), an enterovirus in the familyPicornaviridae, induces cytopathic changes in cell culture systems and directly injures multiple susceptible organs and tissues in vivo, including the myocardium, early after infection. Biochemical analysis of the cell death pathway in CVB3-infected HeLa cells demonstrated that the 32-kDa proform of caspase 3 is cleaved subsequent to the degenerative morphological changes seen in infected HeLa cells. Caspase activation assays confirm that the cleaved caspase 3 is proteolytically active. The caspase 3 substrates poly(ADP-ribose) polymerase, a DNA repair enzyme, and DNA fragmentation factor, a cytoplasmic inhibitor of an endonuclease responsible for DNA fragmentation, were degraded at 9 h following infection, yielding their characteristic cleavage fragments. Inhibition of caspase activation by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD.fmk) did not inhibit the virus-induced cytopathic effect, while inhibition of caspase activation by ZVAD.fmk in control apoptotic cells induced by treatment with the porphyrin photosensitizer benzoporphyrin derivative monoacid ring A and visible light inhibited the apoptotic phenotype. Caspase activation and cleavage of substrates may not be responsible for the characteristic cytopathic effect produced by picornavirus infection yet may be related to late-stage alterations of cellular homeostatic processes and structural integrity.