Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebral Maturation in IUGR and Appropriate for Gestational Age Preterm Babies

Intrauterine growth restriction (IUGR) is associated with increased risk of perinatal morbidity and mortality, as well as long-term neurological deficits. However, neurostructural correlations with observed developmental disabilities have not yet been established. Magnetic resonance imaging (MRI) could prove useful for assessing brain development in the early neonatal period. We evaluated cerebral lesions and morphological maturation by MRIs in 59 preterm neonates, in order to verify the hypothesis that IUGR interferes on human brain development. A total of 26 pregnancies were complicated by IUGR and 33 pregnancies delivered preterm at a comparable gestational age with appropriate for gestational age (AGA). Magnetic resonance examination was performed at the completion of 41 weeks' gestation. White matter disease studied with MR included periventricular cavitations and punctuate lesions characterized by increased signal on T1-weighted and decreased signal on T2-weighted images. Cerebral maturation was defined by the total maturation score, on the basis of 4 morphological parameters of cerebral maturation: myelination (M), cortical infolding (C), germinal matrix distribution (GM), and glial cell migration pattern (G). No difference in brain lesions and in the level of cerebral maturation was found between preterm AGA and IUGR neonates. However, myelination was significantly reduced in IUGR neonates with brain sparing compared to IUGR neonates with normal Doppler of middle cerebral artery. Our study could not demonstrate any major significant difference between preterm AGA and IUGR neonates in terms of lesion occurrence and cerebral maturation. We observed, however, a mild delay in myelination in IUGR with brain sparing in utero. The relevance of this finding needs to be investigated with long-term follow-up.
Alpha 1-Antitrypsin Deficiency in the Fibromyalgia Syndrome

The cup is full in this issue of the Journal of Musculoskeletal Pain [JMP]. Every one of the research contributions warrants some introductory comment, but, as usual, the emphasis of thiseditorialwillbeon the leadmanuscript. From the north of Spain, Blanco and colleagues (1) expand upon their earlier findings (2,3) regarding the relevance of alpha1-antitrypsin [AAT] deficiency [AATD] to the symptoms of the fibromyalgia syndrome [FMS]. In their first report (2), they described two sisters with mild pulmonary symptoms but severe FMS, in a family with life-threatening hereditary homozygous PI ZZ AATD. Their FMS symptoms improved dramatically with weekly intravenous infusions of commercial purified humanAAT[Prolastin®,originally fromBayer HealthCare Biological Products Division, now available from Talecris Biotherapeutics, Research Triangle Park, NC 27709 USA, www. talecris.com]. For six years [1992-1998], these two women maintained good control of their FMS symptoms with continuous AAT therapy. Then, in 1998, there was a worldwide shortage of commercial AAT that required rationing. The sisters still received AAT infusions during the fall and winter months, but for five years, they had none during the four to six months of spring and summer. Each year, when they were withdrawn from the treatment, the two women experienced an exacerbation of their FMS symptoms, which again resolved soon after resuming the weekly infusions. In their second publication on this topic (3), the Spanish authors attempted to develop a mechanism that would explain an association of FMS with AATD. They concluded by suggesting future researchdirections:1. todevelop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FMS patients, 2. to implement a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FMS, 3. to identify specific laboratory markers for diagnostic and clinical evaluation approaches in FMS, 4. to apply the newest medical imaging techniques for diagnosis, and 5. to identify genetic, famil-
Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis

Endometriosis is an estrogen-dependent disease. Steroidogenic factor 1 (SF-1), a transcription factor, is essential for the activation of multiple steroidogenic genes for estrogen biosynthesis in endometriosis-derived stromal cells. Objective: Unravel the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells. DESIGN: We identified a novel CpG island in the SF-1 gene, which spans from exon II to intron III. We evaluated the methylation status of this CpG island. PATIENTS: Eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries (n = 8). None of the patients had received any preoperative hormonal therapy. Stromal cells were isolated from these 2 types of tissues. Results: SF-1 messenger RNA (mRNA) levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells. Bisulfite sequencing showed strikingly increased methylation in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between mRNA levels and percentage methylation of the exon II/intron III are observed. Specifically, the Pearson correlation coefficient was . 98 (P < .001) for this association. Conclusions: We demonstrated that methylation of a coding exon/intron sequence in the SF-1 gene positively regulated its expression in endometriosis, whereas its hypomethylation in normal endometrium was associated with drastically lower SF-1 levels.
Host Species Barriers to Jaagsiekte Sheep Retrovirus Replication and Carcinogenesis

ABSTRACT Understanding the factors governing host species barriers to virus transmission has added significantly to our appreciation of virus pathogenesis. Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. In this study, in order to further clarify the pathogenesis of OPA, we investigated whether goats are resistant to JSRV replication and carcinogenesis. We found that JSRV induces lung tumors in goats with macroscopic and histopathological features that dramatically differ from those in sheep. However, the origins of the tumor cells in the two species are identical. Interestingly, in experimentally infected lambs and goat kids, we revealed major differences in the number of virus-infected cells at early stages of infection. These differences were not related to the number of available target cells for virus infection and cell transformation or the presence of a host-specific immune response toward JSRV. Indeed, we also found that goats possess transcriptionally active endogenous retroviruses (enJSRVs) that likely influence the host immune response toward the exogenous JSRV. Overall, these results suggest that goat cells, or at least those cells targeted for viral carcinogenesis, are not permissive to virus replication but can be transformed by JSRV.
Mechanism of Programmed Obesity in Intrauterine Fetal Growth Restricted Offspring: Paradoxically Enhanced Appetite Stimulation in Fed and Fasting States

We have shown that intrauterine fetal growth restriction (IUGR) newborn rats exhibit hyperphagia, reduced satiety, and adult obesity. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a principal metabolic regulator that specifically regulates appetite in the hypothalamic arcuate nucleus (ARC). In response to fasting, upregulated AMPK activity increases the expression of orexigenic (neuropeptide Y [NPY] and agouti-related protein [AgRP]) and decreases anorexigenic (proopiomelanocortin [POMC]) peptides. We hypothesized that IUGR offspring would exhibit upregulated hypothalamic AMPK, contributing to hyperphagia and obesity. We determined AMPK activity and appetite-modulating peptides (NPY and POMC) during fasting and fed conditions in the ARC of adult IUGR and control females. Pregnant rats were fed ad libitum diet (control) or were 50% food restricted from gestation day 10 to 21 to produce IUGR newborns. At 10 months of age, hypothalamic ARC was dissected from fasted (48 hours) and fed control and IUGR females. Arcuate nucleus messenger RNA ([mRNA] NPY, AgRP, and POMC) and protein expression (total and phosphorylated AMPK, Akt) was determined by quantitative reverse transcriptase–polymerase chain reaction and Western Blot, respectively. In the fed state, IUGR adult females demonstrated evidence of persistent appetite stimulation with significantly upregulated phospho (Thr172)-AMPKα/AMPK (1.3-fold), NPY/AgRP (2.3/1.8-fold) and decreased pAkt/Akt (0.6-fold) and POMC (0.7-fold) as compared to fed controls. In controls though not IUGR adult females, fasting significantly increased pAMPK/AMPK, NPY, and AgRP and decreased pAkt/Akt and POMC. Despite obesity, fed IUGR adult females exhibit upregulated AMPK activity and appetite stimulatory factors, similar to that exhibited by fasting controls. These results suggest that an enhanced appetite drive in both fed and fasting states contributes to hyperphagia and obesity in IUGR offspring.
The Effect of an Animal-Assisted Intervention on Anxiety and Pain in Hospitalized Children

ABSTRACT Forty children between the ages of 8 and 18 years, who were admitted to a hospital pediatric unit, were randomly assigned to an animal-assisted intervention (AAI) or an active control condition (working on an age-appropriate jigsaw puzzle). Ratings of pain and anxiety were taken both pre- and post-condition. The attachment Questionnaire and Family Life Space Diagram (FLSD) also were administered, and information on medications taken was recorded. A significant post-condition difference was found between groups for anxiety, with the aaI group having lower anxiety scores. However, no significant within- or between-group pre-post changes in either pain or anxiety were detected. Nearly two-thirds of the children (64%) reporting pain at baseline were receiving some type of analgesic, which may have influenced outcomes. Findings demonstrate some support that attachment may be a moderating variable: children with a secure attachment style reported lower pain and anxiety at baseline, with large effect sizes for differences in both anxiety (g = 1.34) and pain (g = 1.23). Although the aaI did not significantly reduce anxiety and pain in these hospitalized children, further investigation of the influence of analgesic use and the moderating effect of attachment style is indicated.
Entry of Tiger Frog Virus (an Iridovirus) into HepG2 Cells via a pH-Dependent, Atypical, Caveola-Mediated Endocytosis Pathway

ABSTRACT Tiger frog virus (TFV), in the genus Ranavirus of the family Iridoviridae, causes high mortality of cultured tiger frog tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH4Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.
Camera-based calibration techniques for seamless multiprojector displays

Multiprojector, large-scale displays are used in scientific visualization, virtual reality, and other visually intensive applications. In recent years, a number of camera-based computer vision techniques have been proposed to register the geometry and color of tiled projection-based display. These automated techniques use cameras to "calibrate" display geometry and photometry, computing per-projector corrective warps and intensity corrections that are necessary to produce seamless imagery across projector mosaics. These techniques replace the traditional labor-intensive manual alignment and maintenance steps, making such displays cost-effective, flexible, and accessible. In this paper, we present a survey of different camera-based geometric and photometric registration techniques reported in the literature to date. We discuss several techniques that have been proposed and demonstrated, each addressing particular display configurations and modes of operation. We overview each of these approaches and discuss their advantages and disadvantages. We examine techniques that address registration on both planar (video walls) and arbitrary display surfaces and photometric correction for different kinds of display surfaces. We conclude with a discussion of the remaining challenges and research opportunities for multiprojector displays
Early Steps of the Virus Replication Cycle Are Inhibited in Prostate Cancer Cells Resistant to Oncolytic Vesicular Stomatitis Virus

ABSTRACT Vesicular stomatitis virus (VSV) is currently being studied as a candidate oncolytic virus for tumor therapies due to its potent tumoricidal activity. Previous studies have demonstrated that VSV selectively infects tumor cells due to defects in their antiviral pathways. These defects make them more susceptible to VSV-induced killing than normal cells. However, some cancer cells display differential sensitivity to VSV. Specifically, LNCaP prostate cancer cells are sensitive to infection with VSV, while PC3 prostate cancer cells are relatively resistant to VSV. This suggests that tumor cells vary in the extent to which they develop defects in antiviral pathways and, thus, permit virus replication. The goal of these studies was to identify the step(s) of the viral replication cycle that is inhibited in PC3 cells. Results showed that although attachment of VSV was not significantly different among cell types, penetration was delayed by 10 to 30 min in PC3 cells relative to LNCaP cells. Primary transcription was delayed by 6 to 8 h in PC3 cells relative to LNCaP cells. Similarly, both secondary transcription and viral protein synthesis rates were delayed by about 6 to 8 h. The progressively increasing delay suggests that more than one step is affected in PC3 cells. Analysis of cellular gene expression showed that in contrast to LNCaP cells, PC3 cells constitutively expressed numerous antiviral gene products, which may enhance their resistance to VSV. These data indicate that the use of VSV for oncolytic virus therapy for prostate tumors may require prescreening of tumors for their level of susceptibility.
A scalable wavelet image coding scheme using multi-stage pruned tree-structured vector quantization

A hierarchical pruned tree-structured vector quantizer (PTSVQ) employing multi-stage PTSVQ's is introduced to encode image wavelet coefficients. The result is a low-complexity and scalable image coding system. The effects of non-square selection of the block sizes and normalization on the performance of the system are investigated.
The Influence of Overweight and Obesity on Maternal Soluble fms-Like Tyrosine Kinase 1 and Its Relationship With Leptin During Pregnancy

We studied obesity-related differences in the relation of maternal levels of leptin to levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein that influences placentation and risk of adverse pregnancy outcomes. In a prospective cohort of 286 gravidas, we measured maternal serum levels of sFlt1 and leptin at 5 time points across pregnancy. Analyses stratified on prepregnancy body mass index (<25 vs ≥25) were done using mixed linear models. The mean leptin concentrations were significantly higher in overweight/obese compared to normal-weight women, while mean sFlt1 levels in second and third trimester were significantly higher in normal weight compared to overweight/obese women. The relationship between sFlt1 and leptin differed between the 2 strata. After controlling for maternal weight, a 1 ng/mL increase in leptin was associated with an 19.4 pg/mL increase in sFlt1 (P = .01) in normal-weight women, while leptin was not associated with sFlt1 (β = 1.1, P = .75) in overweight/obese women. Such differences suggest that metabolic differences in overweight/obese women compared to their normal weight peers may differentially impact the physiologic changes during pregnancy.
Isolate-Specific Differences in the Conformational Dynamics and Antigenicity of HIV-1 gp120

ABSTRACT The HIV-1 envelope glycoprotein (Env) mediates viral entry into host cells and is the sole target of neutralizing antibodies. Much of the sequence diversity in the HIV-1 genome is concentrated within Env, particularly within its gp120 surface subunit. While dramatic functional diversity exists among HIV-1 Env isolates—observable even in the context of monomeric gp120 proteins as differences in antigenicity and immunogenicity—we have little understanding of the structural features that distinguish Env isolates and lead to isolate-specific functional differences, as crystal structures of truncated gp120 “core” proteins from diverse isolates reveal a high level of structural conservation. Because gp120 proteins are used as prospective vaccine immunogens, it is critical to understand the structural factors that influence their reactivity with antibodies. Here, we studied four full-length, glycosylated gp120 monomers from diverse HIV-1 isolates by using small-angle X-ray scattering (SAXS) to probe the overall subunit morphology and hydrogen/deuterium-exchange with mass spectrometry (HDX-MS) to characterize the local structural order of each gp120. We observed that while the overall subunit architecture was similar among isolates by SAXS, dramatic isolate-specific differences in the conformational stability of gp120 were evident by HDX-MS. These differences persisted even with the CD4 receptor bound. Furthermore, surface plasmon resonance (SPR) and enzyme-linked immunosorbance assays (ELISAs) showed that disorder was associated with poorer recognition by antibodies targeting conserved conformational epitopes. These data provide additional insight into the structural determinants of gp120 antigenicity and suggest that conformational dynamics should be considered in the selection and design of optimized Env immunogens.
Graph Drawing Aesthetics—Created by Users, Not Algorithms

Prior empirical work on layout aesthetics for graph drawing algorithms has concentrated on the interpretation of existing graph drawings. We report on experiments which focus on the creation and layout of graph drawings: participants were asked to draw graphs based on adjacency lists, and to lay them out "nicely. ” Two interaction methods were used for creating the drawings: a sketch interface which allows for easy, natural hand movements, and a formal point-and-click interface similar to a typical graph editing system. We find, in common with many other studies, that removing edge crossings is the most significant aesthetic, but also discover that aligning nodes and edges to an underlying grid is important. We observe that the aesthetics favored by participants during creation of a graph drawing are often not evident in the final product and that the participants did not make a clear distinction between the processes of creation and layout. Our results suggest that graph drawing systems should integrate automatic layout with the user's manual editing process, and provide facilities to support grid-based graph creation.
Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2

ABSTRACT The distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent probes of different colors, and the cell-cell fusion between these cells was tested. Results indicate that TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell, as found for influenza A virus and metapneumoviruses. This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells. Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection.
Clomiphene for the Treatment of Male Infertility

Male infertility is a relatively common condition caused by low sperm production, immobile sperm, or blockages that prevent the delivery of sperm. This condition can be caused by a variety of illnesses, injuries, chronic health problems, lifestyle choices, other factors, or idiopathic, in which abnormal semen parameters occur without an identifiable cause. Medical management traditionally focuses on correcting endocrine abnormalities related to hormone deficiencies. Clomiphene citrate is an antiestrogen thought to increase sperm parameters in males attempting to conceive. The objective of this review was to evaluate the efficacy and safety of clomiphene citrate in the treatment of male patients with infertility. A literature search of MEDLINE (1966-June 2012) and EMBASE (1980-June 2012) was conducted using the medical terms clomiphene and male infertility and 9 clinical studies were identified. Overall, only 1 study detected a statistically significant benefit on the pregnancy rate in the clomiphene group; however, the majority of the studies demonstrated a statistically significant increase in sperm concentrations. At doses used to treat male infertility, clomiphene was well tolerated with no identified serious adverse effects. Based on the reviewed studies there is insufficient evidence to indicate that clomiphene is effective for the treatment of male infertility.