Miracle-dz/UniFAR-FTUs huggingface dataset:
Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes

Objective:The aim of this study was to establish the gynecological effects of 5 years of treatment with lasofoxifene versus placebo in postmenopausal osteoporotic women. Methods:A total of 8,556 women aged 59 to 80 years with femoral neck or spine bone mineral density T scores of −2.5 or lower were randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or placebo, for 5 years. Results:Endometrial cancer was confirmed for two women in each lasofoxifene group and for three women in the placebo group. Endometrial hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25 mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo), and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo, respectively. Lasofoxifene treatment resulted in a small increase in endometrial thickness versus placebo (least-squares mean change from baseline 1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and −0.72 mm for 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women required surgery for pelvic organ prolapse or urinary incontinence in the placebo and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group: 1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%, 5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene 0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively. Conclusion:These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women.
`What is expressed is not always what is felt': coping with stigma and the embodiment of perceived illegitimacy of multiple sclerosis

Objective: In this study, we investigated the stigma experienced by people with multiple sclerosis (MS) and their relatives. We describe coping as impression management of the body to counteract stigma and illegitimacy. Methods: Fourteen people, including those with MS in the middle and later stages of illness, and their relatives were informally interviewed. The interviews were tape-recorded, subsequently yielding a 500-page document. Results: The findings point to the embodied perception of illegitimacy as a dimension of stigma. Informants reported instrumental and affective advantages of purposefully concealing or informing about their MS to influence social judgement in interpersonal encounters. Discussion: MS sufferers apply a tactic of protective disclosure by which they seek to guard their sense of self. The strategy of preventive disclosure is employed to obtain assistance from others. Furthermore, the strategy of concealing MS is conducted purposefully to prevent the sufferer being deprived of social belonging, especially with regard to work.
Colour spaces in ecology and evolutionary biology

The recognition that animals sense the world in a different way than we do has unlocked important lines of research in ecology and evolutionary biology. In practice, the subjective study of natural stimuli has been permitted by perceptual spaces, which are graphical models of how stimuli are perceived by a given animal. Because colour vision is arguably the best‐known sensory modality in most animals, a diversity of colour spaces are now available to visual ecologists, ranging from generalist and basic models allowing rough but robust predictions on colour perception, to species‐specific, more complex models giving accurate but context‐dependent predictions. Selecting among these models is most often influenced by historical contingencies that have associated models to specific questions and organisms; however, these associations are not always optimal. The aim of this review is to provide visual ecologists with a critical perspective on how models of colour space are built, how well they perform and where their main limitations are with regard to their most frequent uses in ecology and evolutionary biology. We propose a classification of models based on their complexity, defined as whether and how they model the mechanisms of chromatic adaptation and receptor opponency, the nonlinear association between the stimulus and its perception, and whether or not models have been fitted to experimental data. Then, we review the effect of modelling these mechanisms on predictions of colour detection and discrimination, colour conspicuousness, colour diversity and diversification, and for comparing the perception of colour traits between distinct perceivers. While a few rules emerge (e.g. opponent log–linear models should be preferred when analysing very distinct colours), in general model parameters still have poorly known effects. Colour spaces have nonetheless permitted significant advances in ecology and evolutionary biology, and more progress is expected if ecologists compare results between models and perform behavioural experiments more routinely. Such an approach would further contribute to a better understanding of colour vision and its links to the behavioural ecology of animals. While visual ecology is essentially a transfer of knowledge from visual sciences to evolutionary ecology, we hope that the discipline will benefit both fields more evenly in the future.
Blending Face-to-Face Higher Education with Web-Based Lectures: Comparing Different Didactical Application Scenarios

Blended learning as an instructional approach is getting more attention in the educational landscape and has been researched thoroughly. Yet, this study reports the results of an innovation project aiming to gain insight into three different scenarios of applying web-based lectures: as preparation for face-to-face practical exercises, as a repetition of parts of the course, and as an extension of the course. Both the benefits regarding students’ satisfaction, perceived educational effects and the effect on student characteristics were investigated. Results indicate that all students evaluate web-based technology as an added value in higher education. Yet, comparison of the three application scenarios showed that web-based lectures are evaluated most positively when used as course preparation whereas when used as course extension, they were appreciated the least. However, there are indications that student characteristics could play a significant role in the level of appreciation of web-based lectures. We conclude that the potential of web-based lectures lies in their adaptability for use in several scenarios according to educational goals.
Catarrhine phylogeny: noncoding DNA evidence for a diphyletic origin of the mangabeys and for a human-chimpanzee clade.

Maximum-parsimony and maximum-likelihood analyses of two of the serum albumin gene's intron sequences from 24 catarrhines (17 cercopithecid and 7 hominid) and 3 platyrrhines (an outgroup to the catarrhines) yielded results on catarrhine phylogeny that are congruent with those obtained with noncoding sequences of the gamma(1)-gamma(2) globin gene genomic region, using only those flanking and intergenic gamma sequences that in their history were not involved in gene conversion. A data set that combined in a tandem alignment these two sets of noncoding DNA orthologues from the two unlinked nuclear genomic loci yielded the following confirmatory results both on the course of cladistic branchings (the divisions in a cladistic classification of higher ranking taxa into subordinate taxa) and on the ages of the taxa (each taxon representing a clade). The cercopithecid branch of catarrhines, at approximately 14 Ma (mega annum) divided into Colobini (the leaf-eating Old World monkeys) and Cercopithecini (the cheek-pouched Old World monkeys). At approximately 10-9 Ma, Colobini divided into an African clade, Colobina, and an Asian clade, Presbytina; similarly at this time level, Cercopithecini divided into Cercopithecina (the guenons, patas, and green monkeys) and Papionina. At approximately 7 Ma, Papionina divided into Macaca, Cercocebus, and Papio. At approximately 5 Ma, Cercocebus divided subgenerically into C. (Cercocebus) for terrestrial mangabeys and C. (Mandrillus) for drills and mandrills, while at approximately 4 Ma Papio divided subgenerically into P. (Locophocebus) for arboreal mangabeys, P. (Theropithecus) for gelada baboons, and P. (Papio) for hamadryas baboons. In turn, the hominid branch of catarrhines at approximately 18 Ma divided into Hylobatini (gibbons and siamangs) and Hominini; at approximately 14 Ma, Hominini divided into Pongina (orangutans) and Hominina; at approximately 7 Ma, Hominina divided into Gorilla and Homo; and at approximately 6-5 Ma, Homo divided subgenerically into H. (Homo) for humans and H. (Pan) for common and bonobo chimpanzees. Rates of noncoding DNA evolution were assessed using a data set of noncoding gamma sequence orthologues that represented 18 catarrhines, 16 platyrrhines, 3 non-anthropoid primates (2 tarsiers and 1 strepsirhine), and rabbit (as outgroup to the primates). Results obtained with this data set revealed a faster rate of nucleotide substitutions in the early primate lineage to the anthropoid (platyrrhine/catarrhine) ancestor than from that ancestor to the present. Rates were slower in catarrhines than in platyrrhines, slower in the cheek-pouched than in the leaf-eating cercopithecids, and slower yet in the hominids. On relating these results to data on brain sizes and life spans, it was suggested that life-history strategies that favor intelligence and longer life spans also select for decreases in de novo mutation rates.
Lasting cortical activation after repetitive TMS of the motor cortex

Objective: Cerebral [18F]fluorodeoxy-d-glucose PET ([18F]FDG-PET) was used to visualize the lasting neuronal activation after repetitive transcranial magnetic stimulation (rTMS) over the left hand area of the primary motor cortex (M1HAND). Background: Applied over M1HAND, rTMS has been shown to produce a modulation of corticomotor excitability beyond the time of stimulation itself. Methods: Eight right-handed subjects underwent nonquantitative [18F]FDG-PET measurements during two experimental conditions: at rest and after focal subthreshold 5-Hz rTMS over the left M1HAND. In the post-rTMS condition, [18F]FDG was injected immediately after the administration of 1,800 magnetic pulses over the left M1HAND. Relative differences in normalized regional cerebral metabolic rate of glucose (normalized rCMRglc) between conditions were determined using a voxel-by-voxel Student’s t-test and volume-of-interest (VOI) analysis. Analysis was a priori restricted to the M1HAND, the supplementary motor area (SMA), and the primary auditory cortex of both hemispheres. Results: A 5-Hz rTMS of the left M1HAND caused a lasting relative increase in normalized rCMRglc within the M1HAND bilaterally and the SMA. The magnitude and the topographic pattern of persisting relative rCMRglc increases within these motor cortical areas demonstrated considerable interindividual variations. Conclusions: Subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the hand area of the primary motor cortex is associated with a persisting neuronal activation in a distinct set of motor cortical areas beyond the time of stimulation. The current findings demonstrate that [18F]FDG-PET can localize and quantify regional net changes in synaptic cortical activity after rTMS and thus might elucidate the mechanisms underlying rTMS-associated therapeutic effects.
Outdoor stairway segmentation using vertical vanishing point and directional filter

In this paper we propose to detect the localization and recognition of outdoor stairway. This problem is the most fundamental step in solving the problem of autonomous stair climbing navigation. An autonomous system must be able to recognize parameters that can describe stairways in unknown environments. First, we proposed to extract the longest segments of diagonal lines from the edge image in order to identify a set of diagonal line segments candidate. This can provide information itself. Based on the vanishing point we defined the area where the stair candidate is located. We then applied the Gabor filter to detect the horizontal line. Finally, after combining the previous two steps, the algorithm defined the candidate stair area in the image. A set of stair images were used within a variety of conditions in our proposed method. As a result, testing was able to prove its effectiveness.
Preparation and in vitro, in vivo evaluations of norfloxacin-loaded solid lipid nanopartices for oral delivery

This work aims to develop norfloxacin-solid lipid nanoparticles (NFX-SLN) as an oral delivery formulation. Hot homogenization and ultrasonic technique was employed to prepare NFX-SLN using stearic acid as lipid matrix and polyvinyl alcohol as surfactant. The physicochemical characteristics of SLN were investigated by optical microscope scanning electron microscopy and photon correlation spectroscopy. Antibacterial experiments of NFX-SLN were carried out by broth dilution technique. Pharmacokinetics was studied after oral administration in male Sprague-Dawley rats. The results showed that NFX-SLN was spherical and the SLN of the optimized formulation had diameters 301 ± 16.64 nm, polydispersity index 0.15 ± 0.04, zeta potential -30.8 ± 0.69 mv, loading capacity 8.58 ± 0.21% and encapsulation efficiency 92.35 ± 2.24% with good stability at 4 °C. The NFX-SLN had sustained release effect and sustained bactericidal activity. Cytotoxicity studies in cell culture demonstrated that the nanoparticles were not toxic. NFX-SLN resulted in significantly higher plasma drug concentration than native NFX. The SLN increased the relative bioavailability of NFX by 12 folds, prolonged the plasma drug level above the average minimum inhibition concentration from 14 to 168 h. These studies demonstrate that NFX-SLN could be a promising oral formulation for enhanced bioavailability and pharmacological activities.
How is it that infinitary methods can be applied to finitary mathematics? Gödel's T: a case study

Abstract Inspired by Pohlers' local predicativity approach to Pure Proof Theory and Howard's ordinal analysis of bar recursion of type zero we present a short, technically smooth and constructive strong normalization proof for Gödel's system T of primitive recursive functionals of finite types by constructing an ε0-recursive function []0: T → ω so that a reduces to b implies [a]0 > [b]0. The construction of [ ]0 is based on a careful analysis of the Howard-Schütte treatment of Gödel's T and utilizes the collapsing function ψ: ε 0 → ω which has been developed by the author for a local predicativity style proof-theoretic analysis of PA. The construction of [ ]0 is also crucially based on ideas developed in the 1995 paper “A proof of strongly uniform termination for Gödel's T by the method of local predicativity” by the author. The results on complexity bounds for the fragments of T which are obtained in this paper strengthen considerably the results of the 1995 paper. Indeed, for given n let Tn be the subsystem of T in which the recursors have type level less than or equal to n + 2. (By definition, case distinction functionals for every type are also contained in Tn .) As a corollary of the main theorem of this paper we obtain (reobtain? ) optimal bounds for the Tn -derivation lengths in terms of ω+2-descent recursive functions. The derivation lengths of type one functionals from Tn (hence also their computational complexities) are classified optimally in terms of <ω n+2 -descent recursive functions. In particular we obtain (reobtain? ) that the derivation lengths function of a type one functional a ∈ T 0 is primitive recursive, thus any type one functional a in T 0 defines a primitive recursive function. Similarly we also obtain (reobtain? ) a full classification of T 1 in terms of multiple recursion. As proof-theoretic corollaries we reobtain the classification of the IΣ n+1-provably recursive functions. Taking advantage from our finitistic and constructive treatment of the terms of Gödel's T we reobtain additionally (without employing continuous cut elimination techniques) that PRA + PRWO(ε0) ⊢ Π2 0 − Refl(PA) and PRA + PRWO(ω n+2) ⊢ Π2 0 − Refl(IΣ n+1), hence PRA + PRWO(ε0) ⊢ Con(PA) and PRA + PRWO(ω n+2) ⊢ Con(IΣ n+1). For programmatic reasons we outline in the introduction a vision of how to apply a certain type of infinitary methods to questions of finitary mathematics and recursion theory. We also indicate some connections between ordinals, term rewriting, recursion theory and computational complexity.
Genomic imprinting in the placenta

Genomic imprinting is an epigenetic mechanism that is important for the development and function of the extra-embryonic tissues in the mouse. Remarkably all the autosomal genes which were found to be imprinted in the trophoblast (placenta) only are active on the maternal and repressed on the paternal allele. It was shown for several of these genes that their paternal silencing is not dependent on DNA methylation, at least not in its somatic maintenance. Rather, recent studies in the mouse suggest that placenta-specific imprinting involves repressive histone modifications and non-coding RNAs. This mechanism of autosomal imprinting is similar to imprinted X chromosome inactivation in the placenta. Although the underlying reasons remain to be explored, this suggests that imprinting in the placenta and imprinted X inactivation are evolutionarily related.
Sex, infertility and the molecular biology of the androgen receptor

Mutations that totally disrupt androgen receptor function cause the well known testicular feminizing syndrome or complete androgen insensitivity syndrome, wherein a 46 XY individual is completely feminized at birth. Recently it has been increasingly obvious that androgen receptor mutations not only result in the complete androgen insensitivity syndrome, but can cause a wide spectrum of milder insensitivity syndromes including ambiguous genitalia in newborn infants, and ‘idiopathic’ male infertility in otherwise normal males. Characterization of the molecular and structural mechanisms of androgen receptor dysfunction in these cases has led to directed hormonal therapy. Thus the differential response of a Met807Thr mutant androgen receptor to dihydrotestosterone but not testosterone, have been used to restore male genital development in an infant with partial AIS. Of greater significance, because they affect larger numbers of patients, are the mutations and polymorphisms that result in depressed spermatogenesis and male infertility in phenotypic males. Studies involving Singaporean, Australian, North American and Japanese subjects have established that increases in length of a trinucleotide repeat (CAG) tract, encoding a polyglutamine stretch in the transactivation domain of the androgen receptor, are associated with increased risk of defective spermatogenesis and undermasculinization. Independent of the CAG repeats, missense amino-acid substitutions in the ligand-binding domain, involving residues 727, 798 and 886 cause infertility through a novel mechanism. Pathogenicity is transmitted, not through defective ligand binding, but through defective protein-protein interactions between receptor domains and coactivator proteins that are essential for gene transcription. Elucidation of the molecular and structural basis of androgen receptor dysfunction in these cases allows precise genetic counseling and can lead to the design of rational hormonal therapy.
Usefullness of Serum Insulin-Like Growth Factor (IGF-1) and Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) for Colorectal Cancer Diagnosis

Insulin-like growth factor (IGF-1) is a potent mitogen and an anti-apoptotic agent which is regulated by insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 carries IGF-1 through the bloodstream to the target tissues and protects it from proteolytic degradation. IGFBP-3 reduces tumorigenic potential of colon cancer cells in vitro. IGFBP3 may inhibit target cells directly. In the present study, we assessed whether serum levels of IGF-I and IGFBP-3 could be used as tumor markers in patients with colorectal cancers and evaluated its relationship with known tumor markers, carcinoembryogenic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Our study enrolled 40 patients diagnosed with colorectal cancer histopathologically and 40 completely healthy, agematched subjects (control group). Serum IGF-I levels were found significantly higher in patients with colorectal cancers compared to control group (p< 0.01). Serum IGFBP-3 levels were significantly lower in patients with colorectal cancers compared to control group (p< 0.05). The observed increase in CEA and CA19-9 levels in the same subjects were found statistically significantly higher compared to control group (p< 0.05). However, no significant association could be found between change in IGF-1 and IGFBP-3 levels and CEA or CA 19-9. Increased serum levels of IGFI might be considered as a significant predictor of tumor presence in patients with suspected colorectal cancer. Agents that could increase IGFBP-3 levels might be promising for the treatment of colorectal cancers.
Magnetic Behavior of Polycrystalline Gadolinium Subjected to a Magneto-Thermal Protocol

Magneto-thermal (M-T) hysteresis is studied in polycrystalline gadolinium (Gd). The change of the sign of the first anisotropy constant leads to easy cones of magnetization below the spin-reorientation temperature (<inline-formula> <tex-math notation="LaTeX">$T_{\mathrm {SR}} = 250$ </tex-math></inline-formula> K). Cooling a polycrystalline Gd sample in a magnetic field through the spin-reorientation temperature creates magnetic structures which persist to temperatures close to the Curie temperature, if these structures are not erased by going to fields larger than the cooling field. An M-T protocol is applied to give some systematics to these complex processes.
Paroxetine: pharmacokinetic and antidepressant effect in the elderly

To evaluate the pharmacokinetic properties, efficacy, and tolerability of paroxetine in elderly depressed patients, a clinical study was set up ‐ initially at Aalborg Psychiatric Hospital in Denmark, and subsequently at the University Hospital in Linköping, Sweden. A total of 21 patients with a median age of 72 years were included in the study. After a single dose of 20 or 30mg of paroxetine followed by two drug‐free days, treatment continued with 20 or 30mg daily for seven weeks. The majority of patients showed a continuous reduction in their HAMD scores, starting in the second week of treatment. Paroxetine was well tolerated at the doses given, and side‐effects were mostly mild and transient. Steady‐state, pre‐dose plasma levels of paroxetine showed considerable variability, and the median steady‐state concentration was higher in elderly patients compared with data from a previous study in young volunteers. Elimination half‐lives also showed variability between these elderly patients, but tended to be longer after cessation of multiple dosing than after a single dose. They also tended to be longer than in the young volunteers. The results of this study do not advocate reduced doses of paroxetine in the elderly, but further studies are warranted.