Miracle-dz/UniFAR-FTUs huggingface dataset:
Anogenital distance as a marker of androgen exposure in humans

Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a ‘testicular dysgenesis syndrome’. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well‐defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD.
Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.
A novel multi-lane detection and tracking system

In this paper a novel spline-based multi-lane detection and tracking system is proposed. Reliable lane detection and tracking is an important component of lane departure warning systems, lane keeping support systems or lane change assistance systems. The major novelty of the proposed approach is the usage of the so-called Catmull-Rom spline in combination with the extended Kalman filter tracking. The new spline-based model enables an accurate and flexible modeling of the lane markings. At the same time the application of the extended Kalman filter contributes significantly to the system robustness and stability. There is no assumption about the parallelism or the shapes of the lane markings in our method. The number of lane markings is also not restrained, instead each lane marking is separately modeled and tracked. The system runs on a standard PC in real time (i.e. 30 fps) with WVGA image resolution (752 × 480). The test vehicle has been driven on the roads with challenging scenarios, like worn out lane markings, construction sites, narrow corners, exits and entries of the highways, etc., and good performance has been demonstrated. The quantitative evaluation has been performed using manually annotated video sequences.
Participation of protein kinases and phosphatases in the progesterone‐induced acrosome reaction and calcium influx in human spermatozoa

In human spermatozoa, protein kinases have a role in the acrosome reaction (AR) induced by a variety of stimuli. However, there is disagreement or a lack of information regarding the role of protein kinases and phosphatases in the progesterone (P)‐induced increase in intracellular calcium concentration ([Ca2+]i). In addition, there are no studies regarding the role of Ser/Thr and Tyr phosphatases and there are contradictory results regarding the role of Tyr kinases in the P‐induced acrosome reaction. Here, we performed a simultaneous evaluation of the involvement of protein kinases and phosphatases in the P‐induced acrosome reaction and in the P‐induced calcium influx. Motile spermatozoa were capacitated for 18 h and different aliquots were allocated to treated or control groups and then evaluated for their ability to undergo the acrosome reaction and to increase [Ca2+]i in response to P. The acrosome reaction was evaluated using Pisum sativum agglutinin (PSA)‐FITC, and [Ca2+]i was evaluated using fura 2AM. At all of the concentrations tested, PKA inhibitors significantly reduced the percentage of the P‐induced acrosome reaction (p < 0.001). However, only the highest concentrations of PKA inhibitors reduced the P‐induced calcium influx; lower concentrations of PKA inhibitors did not affect it. Similar results were apparent for PKC inhibitors and for tyrosine kinase inhibitors. None of the Ser/Thr phosphatase inhibitors affected the P‐induced acrosome reaction or the P‐induced calcium influx, except for the PP2B inhibitors that significantly reduced the P‐induced acrosome reaction without affecting calcium influx. Finally, the protein tyrosine phosphatase inhibitors significantly blocked the P‐induced acrosome reaction and reduced the amplitude of the P‐induced calcium transient (p < 0.001) as well as the amplitude of the plateau phase (p < 0.01). The data suggest that protein kinases and possibly PP2B have a role on the acrosome reaction at some point downstream of calcium entry and that Tyr phosphatases have a role on the acrosome reaction upstream of calcium entry.
Erectile dysfunction patients are more satisfied with penile prosthesis implantation compared with tadalafil and intracavernosal injection treatments

There are various treatment modalities for erectile dysfunction with different success and satisfaction rates. We aim to compare patient satisfaction with tadalafil, intracavernosal injection, and penile prosthesis implantation in patients with erectile dysfunction. The records of 3448 men with erectile dysfunction were evaluated retrospectively. A total of 356 men with organic erectile dysfunction were enrolled into this study. Of these patients, 132 (37%) received tadalafil 20 mg twice a week for 12 weeks, 106 (30%) patients received tadalafil 5 mg once‐daily for 12 weeks, 96 (27%) patients used intracavernosal injection therapy (Bi‐mix; papaverine and phentolamine). Moreover, 22 patients underwent penile prosthesis implantation. Patient and partner satisfaction were assessed with International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Patients’ mean age was 52.4 ± 25.76 (32–71). The etiology of erectile dysfunction was chronic systemic diseases in 133 (44%) and radical prostatectomy in 121 patients (40%). The mean IIEF‐5 scores improvement after the treatment was higher in penile prosthesis implantation group (12.4 ± 1.3) compared with tadalafil 5 mg (6.7 ± 1.5) (p < 0.01), tadalafil 20 mg (6.2 ± 1.5) (p < 0.01), and intracavernosal injection group (8.4 ± 3.2) (p < 0.05). The EDITS score was significantly higher in penile prosthesis implantation group (78.2 ± 11.3) compared with intracavernosal injection (60.3 ± 6.3), tadalafil 5 mg (72.5 ± 4.5), and tadalafil 20 mg 70.7 ± 3.4 groups (p < 0.05). Partners’ EDITS scores were 70.1 ± 10 in penile prosthesis implantation group, 50.2 ± 1.5 in intracavernosal injection group, 62.9 ± 7.8 in tadalafil 5 mg, and 61.3 ± 5.3 in tadalafil 20 mg group (p < 0.05). Erectile dysfunction patients who underwent penile prosthesis implantation seem to be more satisfied compared with tadalafil treatment and intracavernosal injection. Future clinical trials are warranted to confirm our results.
Molecular Mechanisms of TRPV4‐Mediated Neural Signaling

In signal transduction of metazoan cells, ion channels of the family of transient receptor potential (TRP) have been identified to respond to diverse external and internal stimuli, among them osmotic stimuli. This review highlights a specific member of the TRPV subfamily, the TRPV4 channel, initially named vanilloid‐receptor related osmotically activated channel (VR‐OAC) or OTRPC4. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue osmo‐ and mechanosensory deficits of the TRPV mutant strain osm‐9 in Caenorhabditis elegans. This is an astounding finding given the <26% orthology between OSM‐9 and TRPV4 proteins. Here, recent findings pertaining to TRPV4's mechano‐ and osmosensory function in endothelia, in the alveolar unit of the lung, and in intestinal sensory innervation are reviewed, namely, transduction of mechanical shear stress in endothelia, maintenance of alveolar integrity on the endothelial side, and intestinal mechanosensation of noxious stimuli by dorsal root ganglion sensory neurons, which can be potently sensitized to mechanical stimuli by activation of the proteinase‐activated receptor 2 (PAR‐2), in a strictly TRPV4‐dependent manner.
The Vasoactive Intestinal Peptide Gene Is a Key Modulator of Pulmonary Vascular Remodeling and Inflammation

Pulmonary vascular remodeling and inflammation often coexist in clinical and experimentally induced pulmonary arterial hypertension (PAH). In some instances, the pulmonary hypertension may be the primary, or at least the initial, problem, while inflammatory or autoimmune responses appear to initiate or dominate the picture in other cases. Based on studies in a model of PAH resulting from targeted deletion of the neuropeptide vasoactive intestinal peptide (VIP) gene, we propose that, at least in this experimental model, but possibly also in other situations, both vascular remodeling and inflammation may be mediated by one and the same mechanism: uncontrolled activation of calcineurin–NFAT (nuclear factor of activated T cells) signaling. If this hypothesis is validated, VIP would emerge as an endogenous modulator of pulmonary vascular remodeling and inflammation, through its suppression of NFAT activation.
Regulation of development of rat stem and progenitor Leydig cells by activin

Stem Leydig cells have been demonstrated to differentiate into adult Leydig cells via intermediate stages of progenitor and immature Leydig cells. However, the exact regulatory mechanisms are unclear. We hypothesized that the development of stem or progenitor Leydig cells depends upon locally produced growth factors. Microarray analysis revealed that the expression levels of activin type I receptor (Acvr1) and activin A receptor type II‐like 1 (Acvrl1) were stem > progenitor = immature = adult Leydig cells. This indicates that their ligand activin might play an important role in stem and progenitor Leydig cell proliferation and differentiation. When seminiferous tubules were incubated with 1 or 10 ng/mL activin A for 3 days, it concentration‐dependently increased EdU incorporation into stem Leydig cells by up to 20‐fold. When progenitor Leydig cells were incubated with 1 or 10 ng/mL activin A for 2 days, it concentration‐dependently increased 3H‐thymidine incorporation into progenitor Leydig cells by up to 200%. Real‐time PCR analysis showed that activin A primarily increased Pcna expression but reduced Star, Hsd3b1, and Cyp17a1 expression levels. Activin A also significantly inhibited the basal and luteinizing hormone‐stimulated androgen production. In conclusion, activin A primarily stimulates the proliferation of stem and progenitor Leydig cells, but inhibits the differentiation of stem and progenitor Leydig cells into the Leydig cell lineage in rat testis.
A Preliminary Analysis of Microbial and Biochemical Properties of High‐Temperature Compost

We investigated the microbial community of a high‐temperature compost process exhibiting an internal temperature exceeding 90°C. The waste pile was crosscut and samples were collected from the bottom to the top of the refuse pile. PCR–denaturing gradient gel electrophoresis analysis suggested that the microbial community of the high‐temperature compost is heterogeneous and differs from one locality to another. Heat‐stable collagenases and amylases were extracted directly from the compost pile. Collagenases were located in the upper half of the pile, whereas amylases were detected mainly in the lower parts. Several extremely thermophilic strains were isolated at 80°C; these strains were aerobes. Based on 16S rRNA sequence analysis, the isolates clustered together and represent one or two closely related species. We propose that these thermophilic isolates belong to a novel genus, Caldaterra, gen. nov.
Adaptive steering control for autonomous lane change maneuver

In this paper, we present a two-layer nonlinear adaptive steering controller for autonomous lane change maneuver with respect to a stopped vehicle. First, we derive a dynamic model of the vehicle using the Boltzmann-Hamel method in quasi-coordinates for nonholonomic systems. The lane change maneuver is investigated as a tracking problem with respect to desired cycloidal trajectory, which is generated in real time. An adaptive update control law is designed that allows tracking the desired trajectories in the presence of unknown inertial parameters of the vehicle. Simulation results illustrate the performance of the proposed controller.
Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?

The so‐called “endocrine disruption hypothesis” suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non‐exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized‐controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well‐designed studies of case–control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures.
Strategic decision making for automated driving on two-lane, one way roads using model predictive control

This paper presents an algorithm for strategic decision making regarding when lane change and overtake manoeuvres are desirable and feasible. By considering the task of driving on two-lane, one-way roads, as the selection of desired lane and velocity profile, the algorithm provides useful results in terms of velocity control as well as a decision variable corresponding to whether a lane change manoeuvre should be performed. The decision process is modelled through a mixed logical dynamical system which is solved through model predictive control using mixed integer program formulation. The performance of the proposed control system is explored through simulations of varying driving scenaria on a two-lane, one-way road, which shows the capability of the system to achieve appropriate longitudinal and lateral control strategies depending on the traffic situation.
Cytokine Response in the Intestinal Mucosa of Hamsters Infected with Taenia solium

Taenia solium grows in experimentally infected hamsters. An inflammatory reaction in the intestinal mucosa surrounding the scolex of the worms is produced. We searched for mRNA of Th1 and Th2 cytokines by in situ hybridization in intestinal biopsies. Hamsters were infected with T. solium cysticerci and necropsied on different days post infection (d.p.i.). Tissue from the small intestine was taken from the area surrounding the tapeworm scolex, fixed, and processed for histology. Antisense probes for the detection of interferon (IFN)‐γ, interleukin (IL)‐4, IL‐5, and IL‐13 were used. Kinetics of each cytokine was defined through detection on specific mRNA by counting the number of positive infected hamsters and of positive cells per 100 enterocytes on different d.p.i. IFN‐γ was detected as of d.p.i. 2; all animals were positive on d.p.i. 4 and 8; and on d.p.i. 16, only 20% were still positive. IL‐13 had a pattern similar to IFN‐γ, but all hamsters remained positive until d.p.i. 16 when the experiment was terminated. IL‐4 was positive in 40% of infected hamsters on d.p.i. 6. On d.p.i. 8, IL‐5 was only detected in 20% but increased to 100% by d.p.i. 16. These data suggest that tapeworms induce a mixed Th1/Th2 response with a polarization toward Th2 at 2 weeks post infection, which may influence the expulsion of worms.
Sweet foods increase breast cancer risk

Regularly eating sweet foods, including biscuits, ice cream, honey, and chocolate, may increase the risk of breast cancer. Results from a large case control study of more than 5000 Italian women have shown that the effects may be significant: “If real, the excess risk for frequent sweet consumption may account for 12% of breast cancer cases in this Italian population and, therefore, is far from negligible on a public health level,” say researchers in a report in Annals of Oncology (published online on 25 October; http://annonc.oxfordjournals.org, doi: 10.1093/annonc/mdj051) Although a number of epidemiological and other studies have looked …
In defence of governance: ethics review and social research

There is a growing body of literature that has sought to undermine systems of ethical regulation, and governance more generally, within the social sciences. In this paper, we argue that any general claim for a system of research ethics governance in social research depends on clarifying the nature of the stake that society has in research. We show that certain accounts of this stake—protecting researchers’ freedoms; ensuring accountability for resources; safeguarding welfare; and supporting democracy—raise relevant ethical considerations that are reasonably contested. However, these accounts cannot underpin a general claim in favour of, or against, a system of research ethics governance. Instead, we defend governance in social research on the grounds that research, as an institutionalised form of enquiry, is a constitutive element of human flourishing, and that society ought to be concerned with the flourishing of its members. We conclude by considering the governance arrangements that follow from, and are justified by, our arguments.
Deep brain stimulation – effects on swallowing function in Parkinson's disease

In patients with Parkinson's disease (PD), deep brain stimulation of the subthalamic nucleus (STN DBS) is well recognized in improving limb function, but the outcome on swallowing function has rarely been studied. The aim of this work was to evaluate the effect of STN DBS on pharyngeal swallowing function in patients with PD using self‐estimation and fiberoptic endoscopic evaluation of swallowing.
From genes to characteristics of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating heterogeneous disease of the central nervous system, probably caused by an interaction of common genetic and environmental factors. Much progress has been made through the last few years in genetic studies of MS, and a growing list of genetic risk factors is now available. Biobanking and large collaborations have been prerequisites for this research, and detailed genetic and molecular characterizations are underway, with hopes for to translating new knowledge about MS pathogenesis and characteristics of the disease to personalized, better treatment options for each patient with MS.
Cognitive impairment in early‐stage non‐demented Parkinson's disease patients

In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease–mild cognitive impairment (PD‐MCI) are common. PD‐MCI is a risk factor for developing PDD. Knowledge of cognition in early‐stages PD is essential in understanding and predicting the dementia process.
Estimating the proportion of intracranial aneurysms likely to be amenable to treatment with the pipeline embolization device

Objective A study was undertaken to estimate the fraction of intracranial aneurysms that might be amenable to treatment with the pipeline embolization device (PED), a current flow diverter device, and to determine the types of aneurysms that are probably not amenable to treatment with this device. Methods A retrospective analysis of 200 consecutive intracranial aneurysms as seen on three-dimensional rotational angiography images was conducted. Based on aneurysm and parent artery morphology, four independent observers experienced in the use of the PED judged the likelihood that a given aneurysm could theoretically be treated with one or more PED using a 5-point scale: grades 1 and 2 indicated amenability to treatment with multiple devices; grade 3 indicated amenability to treatment with one device; and grades 4 and 5 indicated the aneurysm would not be amenable to treatment with the PED. Aneurysms were analyzed on the basis of anatomical factors only. Rupture status was not considered. Interobserver agreement was determined. Results 94 of 200 aneurysms (47%) were judged to be likely to be amenable to treatment with the PED; 50 cases (25%) were judged to be amenable to the use of multiple overlapping devices while, in 44 cases (22%), coverage with a single device was preferred. There was a significant relationship between the location of the aneurysm and the grade of the aneurysm (p<0.0001). Conclusion On the basis of anatomical configuration, nearly half of the aneurysms in this study were likely to be amenable to treatment with the PED.