Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Paternal and Maternal Smoking on Semen Quality of Adolescent Men

Background Maternal smoking during pregnancy has been reported to negatively impact sperm counts of the sons. Sufficient data on the effect of paternal smoking is lacking. Objectives We wished to elucidate the impact of maternal and paternal smoking during pregnancy and current own smoking on reproductive function of the male offspring. Methods Semen parameters including sperm DNA integrity were analyzed in 295 adolescents from the general population close to Malmö, Sweden, recruited for the study during 2008–2010. Information on maternal smoking was obtained from the Swedish Medical Birth Register, and regarding own and paternal smoking from questionnaires. The impacts of maternal, paternal and own smoking were evaluated in a multivariate regression model and by use of models including interaction terms. Totally, three exposures and five outcomes were evaluated. Results In maternally unexposed men, paternal smoking was associated with 46% lower total sperm count (95%CI: 21%, 64%) in maternally unexposed men. Both paternal and maternal smoking were associated with a lower sperm concentration (mean differences: 35%; 95%CI: 8.1%, 55% and 36%; 95%CI: 3.9%, 57%, respectively) if the other parent was a non-smoker. No statistically significant impact of own smoking on semen parameters was seen. Conclusions Prenatal both maternal and paternal smoking were separately associated with some decrease in sperm count in men of whom the other parent was not reported to smoke.
Symbolic Pattern Databases in Heuristic Search Planning

This paper invents symbolic pattern databases (SPDB) to combine two influencing aspects for recent progress in domain-independent action planning, namely heuristic search and model checking. SPDBs are off-line computed dictionaries, generated in symbolic backward traversals of automatically inferred planning space abstractions. The entries of SPDBs serve as heuristic estimates to accelerate explicit and symbolic, approximate and optimal heuristic search planners. Selected experiments highlight that the symbolic representation yields much larger and more accurate pattern databases than the ones generated with explicit methods.
Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population

Background Polyfluoroalkyl chemicals (PFCs) are used commonly in commercial applications and are detected in humans and the environment worldwide. Concern has been raised that they may disrupt lipid and weight regulation. Objectives We investigated the relationship between PFC serum concentrations and lipid and weight outcomes in a large publicly available data set. Methods We analyzed data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) for participants 12–80 years of age. Using linear regression to control for covariates, we studied the association between serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and measures of cholesterol, body size, and insulin resistance. Results We observed a positive association between concentrations of PFOS, PFOA, and PFNA and total and non-high-density cholesterol. We found the opposite for PFHxS. Those in the highest quartile of PFOS exposure had total cholesterol levels 13.4 mg/dL [95% confidence interval (CI), 3.8–23.0] higher than those in the lowest quartile. For PFOA, PFNA, and PFHxS, effect estimates were 9.8 (95% CI, −0.2 to 19.7), 13.9 (95% CI, 1.9–25.9), and −7.0 (95% CI, −13.2 to −0.8), respectively. A similar pattern emerged when exposures were modeled continuously. We saw little evidence of a consistent association with body size or insulin resistance. Conclusions This exploratory cross-sectional study is consistent with other epidemiologic studies in finding a positive association between PFOS and PFOA and cholesterol, despite much lower exposures in NHANES. Results for PFNA and PFHxS are novel, emphasizing the need to study PFCs other than PFOS and PFOA.
Surgical Clip-Related Complications after Radical Prostatectomy

Purpose The aim of this study was to describe the surgical clip-related complications that can occur after open retropubic prostatectomy (RRP), pure laparoscopic prostatectomy (LRP), and robot-assisted laparoscopic radical prostatectomy (RALP). Materials and Methods A database of 641 patients who underwent RRP (n=439), LRP (n=49), and RALP (n=153) at our institution between January 2006 and April 2009 was reviewed to identify patients with complications related to the use of surgical clips. The median follow-up time for the entire cohort was 19.0 months (range, 1-42 months). Results Of the 641 patients, 25 (5.7%), 1 (2.0%), and 2 (1.3%) had a bladder neck contracture after RRP, LRP, and RALP, respectively. Two RRP patients had a bladder stone. In total, 6 patients had surgical clip-related complications. Metal clip migration was associated with 2 (8%) of the 25 RRP cases of bladder neck contracture and both (100%) of the RRP cases of bladder stone. Moreover, both (100%) of the RALP cases of bladder neck contractures were associated with Hem-o-lok clip migration into the anastomotic site. Conclusions Surgical clips are prone to migration and may cause, or significantly contribute to, bladder neck contracture or the formation of bladder stones after radical prostatectomy. These findings also suggest that because the incidence of bladder neck contracture after RALP is low, the migration of Hem-o-lok clips should be suspected when voiding difficulty occurs after RALP.
Regularization for Unsupervised Deep Neural Nets

Unsupervised neural networks, such as restricted Boltzmann machines (RBMs) and deep belief networks (DBNs), are powerful tools for feature selection and pattern recognition tasks. We demonstrate that overfitting occurs in such models just as in deep feedforward neural networks, and discuss possible regularization methods to reduce overfitting. We also propose a "partial" approach to improve the efficiency of Dropout/DropConnect in this scenario, and discuss the theoretical justification of these methods from model convergence and likelihood bounds. Finally, we compare the performance of these methods based on their likelihood and classification error rates for various pattern recognition data sets.
Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine‐induced painful neuropathy in rat

Neuropathic pain accompanies peripheral nerve injury following a variety of insults including metabolic disorders, traumatic injury, and exposure to neurotoxins such as vincristine and taxol. Vincristine, a microtubule depolymerizing drug, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969] Neurology 19:367–374; Holland et al. [1973] Cancer Res. 33:1258–1264). The recent development of an animal model of vincristine‐induced neuropathy provides an opportunity to investigate mechanisms underlying this form of neuropathic pain. Systemic vincristine (100 μg/kg) produces hyperalgesia to mechanical stimuli during the second week of administration, which persists for more than a week (Aley et al. [1996] Neuroscience 73:259–265). To test the hypothesis that changes in microtubule structure in nociceptive sensory neurons accompany vincristine‐induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of vincristine‐treated rats. This study constitutes the first quantitative ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated fiber loss or a decrease in the number of microtubules per axons. There was, however, a significant decrease in microtubule density in unmyelinated axons from vincristine‐treated rats. This decrease in microtubule density was due to a significant increase in the cross‐sectional area of unmyelinated axons, suggesting swelling of axons. In addition, vincristine‐treated axons had significantly fewer microtubules cut in cross‐section and significantly more tangentially oriented microtubules per axon compared to controls. These results suggest that vincristine causes disorganization of the axonal microtubule cytoskeleton, as well as an increase in the caliber of unmyelinated sensory axons. J. Comp. Neurol. 395:481–492, 1998. © 1998 Wiley‐Liss, Inc.
The views of genitourinary medicine (GUM) clinic users on unlinked anonymous testing for HIV: evidence from a pilot study of clinics in two English cities

A study was undertaken of the views of users of two genitourinary medicine (GUM) clinics in England on unlinked anonymous testing (UAT) for HIV. The UAT programme measures the prevalence of HIV in the population, including undiagnosed prevalence, by testing residual blood (from samples taken for clinical purposes) which is anonymised and irreversibly unlinked from the source. 424 clinic users completed an anonymous questionnaire about their knowledge of, and attitudes towards, UAT. Only 1/7 (14%) were aware that blood left over from clinical testing may be tested anonymously for HIV. A large majority (89%) said they would agree to their blood being tested, although 74% wanted the opportunity to consent. These findings indicate broad support for UAT of blood in a group of patients whose samples are included in the HIV surveillance programme. The findings suggest the need for greater attention to be given to the provision of information and, if replicated in a larger survey, may justify a reappraisal of UK policy on UAT.
Deep brain stimulation mechanisms: beyond the concept of local functional inhibition

Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high‐frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high‐frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson’s disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets.
Vitamin-D Receptor ( VDR ) Gene ( Fok-I , TaqI & Apa-I ) Polymorphisms in Healthy Individuals from North Indian Population

Genetic variation in human genome is an emerging resource for studying cancer, a complex set of disease characterized by both environmental and genetic contributions. DNA sequences of the human genome reveal that many genes are polymorphic. In coding or noncoding regions of a specific gene, there may be either a single base pair substitution of one nucleotide (SNPs) for another or a variable number of repeats of a short repetitive DNA sequence. (VNTR). These variations may influence the rate of gene transcription, the stability of the messenger RNA, or the quantity and activity of the resulting protein. Thus, the susceptibility or severity of a number of disorders will be influenced by possession of specific alleles of polymorphic genes. SNPs have gained popularity in recent years and are touted as the genetic markers of choice for the Vitamin-D Receptor (VDR) Gene (Fok-I, Taq-I & Apa-I) Polymorphisms in Healthy Individuals from North Indian Population
Co-evolution and Contradiction: A Diamond Model of Designer-User Interaction

This paper explores how the Engineering Design process might balance conflicting constraints of technical product design and the social demands of users. Building on a generic 2D map for innovation in design from the author’s previous work, a prototype 3D Diamond Model is presented to help structure conversations between Designers and Users – or indeed any other group with apparently opposing aims. In theory, the model draws on the structure of Buddhism (in particular the Mandala of the Five Buddha Families) and managerial cybernetics (in particular Beer’s Viable System Model and his Team Syntegrity protocol), to establish how one’s worldview might evolve and how a common worldview for two teams can be determined. In practise, a Facilitator or Researcher helps Designers and Users achieve their respective aims, and develop a common one. When a common worldview is achieved, conversations and activities can become mutually informing, coevolving and emotionally satisfactory at both the individual and team levels. (Less)
The changing status of ‘filler syllables’ on the way to grammatical morphemes

The appearance of ‘filler syllables’ (called here PAEs, for Prefixed Additional Elements) in the late single-word period is analysed in relation to the emergence of grammatical morphemes, by confronting data from the longitudinal study of one child acquiring French, video- recorded between 1;3.2 and 2;2.6, with four hypotheses making different claims about the kind of language knowledge underlying their production: the DEVICES TO LENGTHEN SINGLE-WORD UTTERANCES, the SYNTACTIC SLOTS, the SELECTIVITY OF OCCURRENCE, and the ORGANIZATION OF SURFACE REGULARITIES hypotheses. The pattern of results concerning the first two to three months' production of PAEs points to the existence of a premorphological period in which PAEs result from the organization of phonoprosodic regularities of the language rather than being constrained by structural rules relative to syntactic slots or to the class of the word they precede. This premorphological period is followed by a protomorphological one in which incipient properties of grammatical morphemes and of word classes start to appear at the same time.
The relationship between the mechanical anisotropy of human cortical bone tissue and its microstructure

By Alejandro A. Espinoza Orías Orthopedics research has made significant advances in the areas of biomechanics, bone implants and bone substitute materials. However, to date there is no definitive model to explain the structure-property relationships in bone as a material to enable better implant designs or to develop a true biomechanical analog of bone. The objective of this investigation was to establish a relationship between the elastic anisotropy of cortical bone tissue and its microstructure. Ultrasonic wave propagation was used to measure stiffness coefficients for specimens sectioned along the length of a human femur. The elastic constants were orthotropic and varied with anatomical location. Stiffness coefficients were generally largest at the midshaft and stiffness anisotropy ratios were largest at the distal and proximal ends. Stiffness coefficients were shown to be correlated as a power law relation to apparent density, but anisotropy ratios were not. These tests were run on four additional human femurs to assess the influence of phenotypes as an exploratory investigation. For the current sample size, it was found that in fact these differences do exist, but the causes are and will remain unknown. Certainly, a much larger sample size is needed in order to state definitive conclusions about the phenotypic variation. Alejandro A. Espinoza Orías Texture analysis was performed on selected samples to measure the orientation distribution of the bone mineral crystals. Inverse pole figures showed that bone mineral crystals had a preferred crystallographic orientation, coincident with the long axis of the femur, which is its principal loading direction. The degree of preferred orientation was represented in Multiples of a Random Distribution (MRD), and correlated to the anisotropy ratios. Variation in elastic anisotropy was shown to be primarily due to the bone mineral orientation. The results found in this work can be used to incorporate anisotropy into structural analysis for bone as a material. To my family, for their extraordinary support and love now and always, this endeavor made this possible. Thanks to your constant encouragement I completed the journey. To my beloved wife, Elena, without your inspiration and understanding, this would have been more uphill than it already was. We made it! To the memory of those family members who left us during this period away from home. I will always remember you.
Comparative mtDNA phylogeography of neotropical freshwater fishes: testing shared history to infer the evolutionary landscape of lower Central America

Historical biogeography seeks to explain contemporary distributions of taxa in the context of intrinsic biological and extrinsic geological and climatic factors. To decipher the relative importance of biological characteristics vs. environmental conditions, it is necessary to ask whether groups of taxa with similar distributions share the same history of diversification. Because all of the taxa will have shared the same climatic and geological history, evidence of shared history across multiple species provides an estimate of the role of extrinsic factors in shaping contemporary biogeographic patterns. Similarly, differences in the records of evolutionary history across species will probably be signatures of biological differences. In this study, we focus on inferring the evolutionary history for geographical populations and closely related species representing three genera of primary freshwater fishes that are widely distributed in lower Central America (LCA) and northwestern Colombia. Analysis of mitochondrial gene trees provides the opportunity for robust tests of shared history across taxa. Moreover, because mtDNA permits inference of the temporal scale of diversification we can test hypotheses regarding the chronological development of the Isthmian corridor linking North and South America. We have focused attention on two issues. First, we show that many of the distinct populations of LCA fishes diverged in a relatively brief period of time thus limiting the phylogenetic signal available for tests of shared history. Second, our results provide reduced evidence of shared history when all drainages are included in the analysis because of inferred dispersion events that obscure the evolutionary history among drainage basins. When we restrict the analysis to areas that harbour endemic mitochondrial lineages, there is evidence of shared history across taxa. We hypothesize that there were two to three distinct waves of invasion into LCA from putative source populations in northwestern Colombia. The first probably happened in the late Miocene, prior to the final emergence of the Isthmus in the mid‐Pliocene; the second was probably coincident with the rise of the Isthmus in the mid‐Pliocene, and the third event occurred more recently, perhaps in the Pleistocene. In each case the geographical scale of the dispersion of lineages was progressively more limited, a pattern we attribute to the continuing development of the landscape due to orogeny and the consequent increase in the insularization of drainage basins. Thus, the fisheye view of LCA suggests a complex biogeographic history of overlaid cycles of colonization, diversification, sorting and extinction of lineages.
Membrane fusion process of Semliki Forest virus. II: Cleavage-dependent reorganization of the spike protein complex controls virus entry

The envelope of the Semliki Forest virus (SFV) contains two transmembrane proteins, E2 and E1, in a heterodimeric complex. The E2 subunit is initially synthesized as a precursor protein p62, which is proteolytically processed to the mature E2 form before virus budding at the plasma membrane. The p62 (E2) protein mediates binding of the heterodimer to the nucleocapsid during virus budding, whereas E1 carries the entry functions of the virus, that is, cell binding and low pH-mediated membrane fusion activity. We have investigated the significance of the cleavage event for the maturation and entry of the virus. To express SFV with an uncleaved p62 phenotype, BHK-21 cells were transfected by electroporation with infectious viral RNA transcribed from a full-length SFV cDNA clone in which the p62 cleavage site had been changed. The uncleaved p62E1 heterodimer was found to be used for the formation of virus particles with an efficiency comparable to the wild type E2E1 form. However, in contrast to the wild type virus, the mutant virus was virtually noninfectious. Noninfectivity resulted from impaired uptake into cells, as well as from the inability of the virus to promote membrane fusion in the mildly acidic conditions of the endosome. This inability could be reversed by mild trypsin treatment, which converted the viral p62E1 form into the mature E2E1 form, or by treating the virus with a pH 4.5 wash, which in contrast to the more mild pH conditions of endosomes, effectively disrupted the p62E1 subunit association. We conclude that the p62 cleavage is not needed for virus budding, but regulates entry functions of the E1 subunit by controlling the heterodimer stability in acidic conditions.
Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography and hysteroscopy

We aimed to compare the accuracy of transvaginal sonography (TVS), saline infusion sonohysterography (SIS) and hysteroscopy (HS) for uterine pathologies among infertile women. A total of 346 patients were selected for operative hysteroscopy, following SIS after TVS. SİS was performed with a Cook Soft 500 IVF catheter. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated to compare the accuracy of TVS, SIS and hysteroscopy for uterine abnormalities. SIS showed a sensitivity of 87%, specificity of 100% and PPV of 100% for endometrial hyperplasia, and a sensitivity and NPV of 100% for polypoid lesions. For submucosal myoma SIS showed a sensitivity of 99% with PPV of 96%. Hysteroscopy had a sensitivity, specificity, PPV and NPV of 98%, 83%, 96% and 91%, respectively for overall uterine pathologies. Finally, SIS seems to be superior to TVS, for uterine pathologies, with respect to hysteroscopy as the gold standard.
Design, Synthesis and Structure-Activity Relationship Studies of Novel Survivin Inhibitors with Potent Anti-Proliferative Properties

The anti-apoptotic protein survivin is highly expressed in most human cancer cells, but has very low expression in normal differentiated cells. Thus survivin is considered as an attractive cancer drug target. Herein we report the design and synthesis of a series of novel survivin inhibitors based on the oxyquinoline scaffold from our recently identified hit compound UC-112. These new analogs were tested against a panel of cancer cell lines including one with multidrug-resistant phenotype. Eight of these new UC-112 analogs showed IC50 values in the nanomole range in anti-proliferative assays. The best three compounds among them along with UC-112 were submitted for NCI-60 cancer cell line screening. The results indicated that structural modification from UC-112 to our best compound 4g has improved activity by four folds (2.2 μM for UC-112 vs. 0.5 μM for 4g, average GI50 values over all cancer cell lines in the NCI-60 panel). Western blot analyses demonstrated the new compounds maintained high selectivity for survivin inhibition over other members in the inhibition of apoptosis protein family. When tested in an A375 human melanoma xenograft model, the most active compound 4g effectively suppressed tumor growth and strongly induced cancer cell apoptosis in tumor tissues. This novel scaffold is promising for the development of selective survivin inhibitors as potential anticancer agents.