Miracle-dz/UniFAR-FTUs huggingface dataset:
The Estimation of Gestational Age at Birth in Database Studies

Background: Studies on the safety of prenatal medication use require valid estimation of the pregnancy duration. However, gestational age is often incompletely recorded in administrative and clinical databases. Our objective was to compare different approaches to estimating the pregnancy duration. Methods: Using data from the Clinical Practice Research Datalink and Hospital Episode Statistics, we examined the following four approaches to estimating missing gestational age: (1) generalized estimating equations for longitudinal data; (2) multiple imputation; (3) estimation based on fetal birth weight and sex; and (4) conventional approaches that assigned a fixed value (39 weeks for all or 39 weeks for full term and 35 weeks for preterm). The gestational age recorded in Hospital Episode Statistics was considered the gold standard. We conducted a simulation study comparing the described approaches in terms of estimated bias and mean square error. Results: A total of 25,929 infants from 22,774 mothers were included in our “gold standard” cohort. The smallest average absolute bias was observed for the generalized estimating equation that included birth weight, while the largest absolute bias occurred when assigning 39-week gestation to all those with missing values. The smallest mean square errors were detected with generalized estimating equations while multiple imputation had the highest mean square errors. Conclusions: The use of generalized estimating equations resulted in the most accurate estimation of missing gestational age when birth weight information was available. In the absence of birth weight, assignment of fixed gestational age based on term/preterm status may be the optimal approach.
SQUAMOSA-PROMOTER BINDING PROTEIN 1 initiates flowering in Antirrhinum majus through the activation of meristem identity genes.

The degree to which developmental genetic pathways are conserved across distantly related organisms is a major question in biology. In Arabidopsis thaliana (L.) Heynh. , inflorescence development is initiated in response to a combination of external and internal floral inductive signals that are perceived across the whole plant, but are integrated within the shoot apical meristem. Recently, it was demonstrated that SQUAMOSA-PROMOTER BINDING PROTEIN (SBP)-box proteins regulate A. thaliana flowering time by mediating signals from the autonomous and photoperiod pathways, and by directly activating key genes involved in inflorescence and floral meristem identity, including FRUITFULL (FUL), APETALA1 (AP1) and LEAFY (LFY). In the distantly related core eudicot species Antirrhinum majus L. , paralogous SBP-box proteins SBP1 and SBP2 have likewise been implicated in regulating the AP1 ortholog SQUAMOSA (SQUA). To test the hypothesis that SBP-box genes are also involved in the floral induction of A. majus, we used a reverse genetic approach to silence SBP1. SBP1-silenced lines are late to nonflowering, and show reduced apical dominance. Furthermore, expression and sequence analyses suggest that the SBP1-mediated transition to flowering occurs through the positive regulation of FUL/LFY homologs. Together, these data outline the utility of virus-induced gene silencing in A. majus, and provide new insight into the conservation of flowering time genetic pathways across core eudicots.
Competence and natural transformation in vibrios

Natural transformation is a major mechanism of horizontal gene transfer in bacteria. By incorporating exogenous DNA elements into chromosomes, bacteria are able to acquire new traits that can enhance their fitness in different environments. Within the past decade, numerous studies have revealed that natural transformation is prevalent among members of the Vibrionaceae, including the pathogen Vibrio cholerae. Four environmental factors: (i) nutrient limitation, (ii) availability of extracellular nucleosides, (iii) high cell density and (iv) the presence of chitin, promote genetic competence and natural transformation in Vibrio cholerae by co‐ordinating expression of the regulators CRP, CytR, HapR and TfoX respectively. Studies of other Vibrionaceae members highlight the general importance of natural transformation within this bacterial family.
Characterization of the lysogenic repressor (c) gene of the Pseudomonas aeruginosa transposable bacteriophage D3112.

Bacteriophage D3112 is a Mu-like temperate transposable phage of Pseudomonas aeruginosa. Genetic mapping and DNA sequence analysis have identified the left end of the phage genome as encoding the transposase enzyme (A) and the lysogenic (c) repressor. The c open reading frame (ORF), located at the leftmost end of the phage genome and transcribed from right to left, has four possible GTG initiation codons. Using site-directed mutagenesis, each of the four GTG codons was modified to GTA, which cannot serve as an initiation codon. Plasmids were constructed expressing either the wild-type repressor ORF or the ORFs containing the mutated GTA codons. When introduced into Pseudomonas aeruginosa, no immunity to superinfection by D3112 was observed when the second GTG had been mutated. Northern blotting analysis demonstrated that the D3112 c repressor is transcribed as a 900-nt mRNA. The promoter region was defined by transcriptional lacZ fusions and primer extension analyses to bp 972-940 from the left end of the phage genome. When the D3112 c repressor was overexpressed and purified as a fusion protein with a C-terminal six-histidine extension (cts15-His6), it showed high affinity for a 261-bp PvuII fragment localized directly upstream of the c repressor ORF. Our results indicate that although D3112 c shows higher amino acid similarity to the lambda family of repressors than it does to those of Mu and D108, it appears that its structure and function more accurately reflect an evolutionary ancestry with those from transposable coliphages Mu and D108.
Transition State Stabilization by a Catalytic RNA

The hairpin ribozyme catalyzes sequence-specific cleavage of RNA through transesterification of the scissile phosphate. Vanadate has previously been used as a transition state mimic of protein enzymes that catalyze the same reaction. Comparison of the 2.2 angstrom resolution structure of a vanadate–hairpin ribozyme complex with structures of precursor and product complexes reveals a rigid active site that makes more hydrogen bonds to the transition state than to the precursor or product. Because of the paucity of RNA functional groups capable of general acid-base or electrostatic catalysis, transition state stabilization is likely to be an important catalytic strategy for ribozymes.
The Effects of the Mennonite Church USA on Enrollment in Mennonite Institutions of Higher Education

Steiner, Katherine M.A., Department of Educational Leadership, College of Education and Human Services, Wright State University, 2010. The Effects of the Mennonite Church USA on Enrollment in Mennonite Institutions of Higher Education. The purpose of this study was to determine if enrollment at Mennonite institutions of higher education was impacted after the Mennonite Church (MC) USA formed in 2002. There are five Mennonite institutions of higher education in the United States: Bethel College in Kansas, Bluffton University in Ohio, Eastern Mennonite University in Virginia, Goshen College in Indiana, and Hesston College in Kansas. This parallel mixed methods study identified how the merger of the MC USA impacted the overall enrollment at Mennonite IHE. In addition, it explored enrollment based on gender, race, or Mennonite affiliation. For the quantitative method of this research, pre-existing data obtained from the Mennonite Education Agency determined the percentage of change in student enrollment between 2003 and 2008. The quantitative results varied though three of the five Mennonite IHE experienced a decline in overall undergraduate enrollment between 2003 and 2008. Qualitatively, this researcher captured the attitudes, perceptions, and professional observations of enrollment professionals at each of the Mennonite IHE through interviews. Common themes in the data indicated the pressure to increase enrollment
Impact of immunoadsorption on xenogeneic extracorporeal pig liver perfusion: assessment of organ function during autologous reperfusion

The shortage of liver grafts has resulted in an intensive search for alternative strategies of liver support in acute liver failure. Extracorporeal perfusion of pig livers (ECLP) is not a new concept, but recent improvements in cardiopulmonary bypass technology and new knowledge about xenogeneic immunologic mechanisms have made it a potential therapeutic modality. In previous suboptimal experimental and clinical models, no statements about the beneficial effect of long‐lasting periods of ECLP were made. The aim of this study was to evaluate the capacity of pig liver for metabolic regeneration after xenogeneic ECLP under largely physiologic conditions. To delay hyperacute rejection (HAR), we utilized immunoadsorption (IA) of naturally preformed xenogeneic antibodies (XNAbs). This led to a stable xenogeneic ECLP for 45 min. However, IA was not able to prevent completely organ damage or loss of function resulting from insufficient autologous reperfusion. The inability to regenerate during autologous reperfusion provides a new measure of the function of a xenogeneic perfused pig liver. In addition, our results implicate that patients with fulminant liver failure will benefit from short perfusions with several fresh organs rather than from long perfusion with a single pig liver.
Effect of training on repeatability of cardiopulmonary exercise performance in normal men and women.

The effect of gender and training on repeatability of cardiopulmonary exercise performance has not been well defined. Therefore, we performed two bicycle exercise tests 1 wk apart in each of two groups: In 19 normal subjects (age 24 to 64 yr, 10 females), with a mean maximal oxygen uptake (VO2max) of 42 mL.kg-1.min-1, who had been in an ongoing training program including bicycle exercise, and in 19 untrained volunteers (23 to 54 yr, 11 females) with a mean VO2max of 36 mL.kg-1.min-1 (P < 0.05). Mean differences in physiologic variables measured during tests 1 and 2 were calculated. Repeatability coefficients were defined as 2 SD in percent of the means. In untrained subjects mean (+/- SD) maximal heart rate decreased by 4 +/- 5 beats.min-1 from the first to the second test (P < 0.05). VO2max and maximal work rate (Wmax) remained unchanged. No significant changes in these or other variables occurred in trained subjects. Repeatability coefficients for VO2max were 8 and 13% in trained and untrained subjects, respectively (P = NS). For Wmax the repeatability coefficient in untrained (11%) exceeded that in trained subjects (4%, P < 0.05). Repeatability coefficients did not differ among males and females. Our study provides normal values for repeatability of various parameters assessed during exercise testing and demonstrates that interpretation of performance during repeated tests has to account for training of the subjects.
Amylin evokes protein p20 phosphorylation and insulin resistance in rat skeletal muscle extensor digitorum longus

In the present study, we investigate effect of amylin on the insulin sensitivity of rat skeletal muscle extensor digitorum longus (EDL) using in vitro intact muscle incubation in combination with metabolic radioactive labeling. The molecular basis of the amylin action was further examined using proteomic analysis. In particular, proteins of interest were characterized using an integrated microcharacterization procedure that involved in-gel trypsin digestion, organic solvent extraction, high performance liquid chromatography separation, microsequencing and microsequence analysis. We found that amylin significantly decreased the insulin-stimulated glucose incorporation into glycogen (p < 0.01) and produced a protein spot of approximately 20 ku in size. This amylin responsive protein (hereby designated as amylin responsive protein 1, APR1) was identified to be protein p20. Moreover, ARP1 spots on gels were found to consistently produce a corresponding radioactive spot on X-ray films in 32Pi but not in 35S-methionine labeling experiments. In conclusion, our results showed that in vitro amylin concomitantly evoked the production of ARP1 and caused insulin resistance in EDL muscle. It is suggested that protein p20 may be involved in amylin signal transduction and the appearance of ARP1 may be a step in a molecular pathway leading to the development of insulin resistance. ARP1 might therefore be a useful molecular marker for amylin action, insulin resistance and Type 2 diabetes.
Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis

Autoimmune pancreatitis is a rare condition which can mimic pancreatic carcinoma. We report the cases of 10 patients with autoimmune pancreatitis investigated in two different centers using contrast-enhanced endosonography. In these patients, contrast-enhanced endosonography showed a unique vascularization pattern which makes it easy to discriminate between autoimmune pancreatitis and lesions caused by pancreatic cancer. Lesions caused by autoimmune pancreatitis and the surrounding pancreas typically showed hypervascularization, whereas lesions caused by pancreatic cancer were hypovascularized. This was true for all patients with the exception of one who showed a normal vascularization pattern in comparison with normal patients and no signs of hypovascularization. Final diagnosis was achieved either by transcutaneous biopsy or a combination of endoscopic fine-needle aspiration with IgG4 immunostaining of the sample. All patients were followed up over a period of at least 12 months to rule out pancreatic carcinoma.
Complete Chromogen Separation and Analysis in Double Immunohistochemical Stains Using Photoshop-based Image Analysis

Simultaneous detection of two different antigens on paraffin-embedded and frozen tissues can be accomplished by double immunohistochemistry. However, many double chromogen systems suffer from signal overlap, precluding definite signal quantification. To separate and quantitatively analyze the different chromogens, we imported images into a Macintosh computer using a CCD camera attached to a diagnostic microscope and used Photoshop software for the recognition, selection, and separation of colors. We show here that Photoshop-based image analysis allows complete separation of chromogens not only on the basis of their RGB spectral characteristics, but also on the basis of information concerning saturation, hue, and luminosity intrinsic to the digitized images. We demonstrate that Photoshop-based image analysis provides superior results compared to color separation using bandpass filters. Quantification of the individual chromogens is then provided by Photoshop using the Histogram command, which supplies information on the luminosity (corresponding to gray levels of black-and-white images) and on the number of pixels as a measure of spatial distribution.
Proteomic identification of rainbow trout blood plasma proteins and their relationship to seminal plasma proteins

The characterisation of fish blood proteomes is important for comparative studies of seminal and blood proteins as well as for the analysis of fish immune mechanisms and pathways. In this study, LC‐MS/MS and 2D‐DIGE were applied to compare rainbow trout seminal (SP) and blood plasma (BP) proteomes. The 54 differentially abundant proteins identified in SP are involved in a variety of signalling pathways, including protein ubiquitination, liver X receptor/retinoid X receptor (LXR/RXR) and farnesoid X receptor activation, cell cycle and acute phase signalling. These findings may indicate the prevalence of acute phase signalling pathways in trout SP, and its essential role in protecting spermatozoa and reproductive tissues. Our study provides the first in‐depth analysis of the trout BP proteome, with a total of 119 proteins identified. The major proteins of rainbow trout BP were recognised as acute phase proteins. Analysis of BP proteins indicated that acute phase response signalling, the complement system, liver X receptor/retinoid X receptor and farnesoid X receptor activation and the coagulation system are the top canonical pathways. This study enhances knowledge of the blood origin of trout SP proteins and understanding of fish reproductive biology. Our results provide new insight into blood proteins specifically important for fish physiology and innate immunity. The mass spectrometry data are available via ProteomeXchange with the identifier PXD005988 and https://doi.org/10.6019/PXD005988.
Intrapulmonary Pharmacokinetics of S-013420, a Novel Bicyclolide Antibacterial, in Healthy Japanese Subjects

ABSTRACT S-013420 (EDP-420) is a novel bicyclolide (bridged bicyclic macrolide) antibacterial currently under development for the treatment of respiratory tract infections. The objective of the present study was to determine the plasma and intrapulmonary pharmacokinetic parameters of orally administered S-013420 in healthy volunteers. Twenty-eight healthy Japanese male subjects who never smoked were randomly allocated to seven groups of four subjects each who underwent bronchoalveolar lavage (BAL) at different times after dosing (2, 4, 6, 8, 10, 12, or 24 h). Blood samples were also taken at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after dosing. The S-013420 concentrations in plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs) were measured by using a combined high-performance liquid chromatography-mass spectrometric technique. A pharmacokinetic analysis of the plasma, ELF, and AM S-013420 concentration profiles was performed. S-013420 was rapidly absorbed in plasma, and the mean time to the maximum concentration in plasma was 2.27 h. S-013420 was rapidly distributed to the ELF and was slowly distributed to AMs. The areas under the concentration-time curves from time zero to 24 h (AUC0-24) for S-013420 were 20.3 times higher in ELF than in plasma and 244.6 times higher in AMs than in plasma. The mean maximum concentration in plasma was higher in ELF than in plasma and was much higher in AM than in plasma. Furthermore, pharmacodynamic calculations were done by using the AUC0-24/MIC90 ratio for common pneumonia pathogens (Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). The AUC0-24 for plasma/MIC90s for these four organisms were 41.8, 83.6, 1.3, and 20.9, respectively. The AUC0-24 for ELF/MIC90s were 849.6, 1,699.2, 26.6, and 424.8, respectively. Considering the good efficacy shown in a subsequent phase 2 study (S. Kohno, K. Yamaguchi, Y. Tanigawara, A. Watanabe, A. Aoki, Y. Niki, and J. Fujita, Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-485), the good distribution of S-013420 in AMs and ELF observed in the present study is predictive of the good efficacy of S-013420 against respiratory pathogens.
Does PET Reconstruction Method Affect Deauville Score in Lymphoma Patients?

When evaluating 18F-FDG PET images with the Deauville score (DS), the quantification of tumor and reference organs limits the problem of optical misinterpretation. Compared with conventional reconstruction algorithms, point-spread function (PSF) modeling increases SUVs significantly in tumors but only moderately in the liver, which could affect the DS. We investigated whether the choice of the reconstruction algorithm affects the DS and whether discordance affects the capability of 18F-FDG PET to stratify lymphoma patients. Methods: Overall, 126 patients with diffuse large B-cell lymphoma were included (56 female and 70 male; median age, 65 y; range, 20–88 y). PET data were reconstructed with the unfiltered PSF method. Additionally, a 6-mm filter was applied to PSF images to meet the requirements of the EANM Research Ltd. (EARL) harmonization program from the European Association of Nuclear Medicine (EANM) (PSFEARL). One hundred interim PET (i-PET) and 95 end-of-treatment PET (EoT-PET) studies were analyzed. SUVmax in the liver and aorta was determined using automatic volumes of interest and compared with SUVmax in the residual mass with the highest 18F-FDG uptake. Results: For i-PET, using PSF and PSFEARL, we classified patients as responders and nonresponders in 60 and 40 cases versus 63 and 37 cases, respectively. Five cases of major discordance (5.0%) occurred (i.e., changes from responder to nonresponder). For Eot-PET, patients were classified using PSF and PSFEARL as responders and nonresponders in 69 and 26 cases versus 72 and 23 cases, respectively. Three cases of major discordance (3.2%) occurred. Concordance (Cohen unweighted κ) between the PSF and the PSFEARL DS was 0.82 (95% confidence interval, 0.73–0.91) for i-PET and 0.89 (95% confidence interval, 0.81–0.96) for EoT-PET. The median follow-up periods were 28.4 and 27.4 mo for i-PET and EoT-PET, respectively. Kaplan–Meier analysis showed statistically significant differences in progression-free survival and overall survival among responders and nonresponders no matter which reconstruction was used for i-PET and EoT-PET. Conclusion: Neither DS nor risk stratification of diffuse large B-cell lymphoma patients is affected by the choice of PET reconstruction. Specifically, the use of PSF is not an issue in routine clinical processes or in multicenter trials. These findings have to be confirmed in escalation and deescalation procedures based on early i-PET.
Visual Acuity, Contrast Sensitivity, Subjective Quality of Vision, and Quality of Life with 4 Different Multifocal IOLs

Purpose This prospective, randomized, double-masked, clinical trial was designed to evaluate visual acuity, contrast sensitivity, subjective quality of vision, and quality of life in 47 patients symmetrically, and randomly, implanted with 4 different IOL designs (SN6AD1, SN60D3, ReZoom NXG1, and Tecnis ZMA00), 3 months after cataract intervention. Methods Binocular corrected and uncorrected distance visual acuity, binocular distance corrected (BCNVA) and uncorrected (UCNVA) near visual acuity, binocular distance corrected (BCIVA) and uncorrected (UCIVA) intermediate visual acuity, photopic, mesopic, and mesopic with glare contrast sensitivity, quality of vision, and quality of life were evaluated. Results Statistically and clinically significant differences were found in BCNVA and UCNVA at 33 cm between high and low add power IOLs, while diffractive SN6AD1 lenses achieved better UCNVA at 40 cm than refractive ReZoom IOLs. Asphericity and low add power were found to improve BCIVA. Contrast sensitivity was similarly compromised in all IOL models, although diffractive optics and aspheric profiles performed better in mesopic conditions. All IOL types received similar overall satisfaction and quality of life scores. Whereas ReZoom patients depended on their spectacles for near tasks, intermediate vision was spectacle independent. Photic phenomena were present in all IOLs, albeit more frequent in ReZoom IOLs. Conclusions The present results, which reflect IOL characteristics in optics, profile, and add power, may contribute to help surgeons decide on the type of IOL most suitable for each patient, especially those with high visual demands at near and intermediate distances.