Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct costs of unintended pregnancy in Spain

Abstract Objective The aim of the study was to estimate the burden and direct medical costs of unintended pregnancy to the public payer in Spain. Methods An economic model evaluating the costs and outcomes of contraceptive use over a 1-year period was constructed for women in Spain aged 15 to 44 years at risk of pregnancy. Model inputs were derived from published literature and national survey data. Outcomes evaluated included: (i) the annual number of unintended pregnancy events and their cost; (ii) the proportion of unintended pregnancy events and their cost due to non-adherence; and (iii) the use and cost of contraceptive methods in Spain. Results Of the total number of pregnancies, 35% are estimated to be unintended and are associated with a direct cost burden of €292.8 million per year. Most unintended pregnancies (26%) occur in women aged 30 to 34 years, whilst 69% of the total cost burden is estimated to be attributable to poor adherence to contraceptive methods. Conclusions The cost associated with unintended pregnancy is high. The major proportion of the burden is estimated to be attributable to imperfect adherence and is likely avoidable. Shifts in patterns of contraceptive use, combined with measures to improve adherence, could have a substantial and positive impact on this burden. Chinese Abstract 摘要： 目的 本研究目的是估算在西班牙意外妊娠给公众纳税人带来的负担和直接医疗费用。 方法 针对西班牙15至44岁有妊娠风险的女性建立一个经济模型，来评价采用避孕措施超过1年的费用和效果。 模型的数据的纳入来自公开发表的文献和国家调查数据。 效果评价包括以下内容：（1）一年意外妊娠事件的数目和相关费用；（2）由于未坚持使用避孕措施而意外怀孕事件的比例和相关费用；（3）在西班牙避孕措施的应用及相关费用。 结果 在总的怀孕人数中，约35%是意外妊娠，与之相关的直接费用负担是每年2. 928亿欧元。 意外妊娠发生率最高的是30-34岁妇女，为26%，同时，据估算，总费用负担的69%是由于没有很好的坚持使用避孕方法。 结论 意外怀孕相关的费用很高。 负担的最主要的部分是由于没有很好地坚持采用避孕措施造成，并且这可能是可以避免的。 改变避孕方法应用的模式，同时采取一些提高依从性的措施，能够对降低负担产生重大的积极的影响。
NUMBER AND DISTRIBUTION OF CAPILLARIES AS DETERMINANTS OF MYOCARDIAL OXYGEN TENSION.

Blood content per gram of tissue was measured in various regions of the myocardium of the dog, by use of I 131 -labeled albumin and Cr 51 O 4 -labeled red cells. The ratio of I 131 to Cr 51 O 4 distributions was uniform, indicating that plasma skimming does not increase O 2 delivery to the inner layers. Gradients in blood content were observed from epicardium to endocardium, and in the base-apex dimension of the heart. Both the transmural gradient and the amount of blood per gram of tissue were greatest at the left ventricular apex. In this region the deeper layers contained 1.5 times as much blood as superficial ones. The data permitted estimates of the number of open capillaries, and of intercapillary distances. These estimates indicate that only a fraction of the available capillaries are perfused at rest. Mean tissue oxygen tensions were computed for various conditions of flow, capillarity, and metabolism by use of the Kety modification of the Krogh equation. Results are discussed in relation to the regulation of tissue PO 2 .
Towards Quantitative Image Reconstruction Using Monte-Carlo Simulations in Multi-Wire Proportional Chamber-Based Small Animal PET

The quadHIDAC is a dedicated high resolution small animal PET scanner based on multi-wire proportional chamber detectors. It provides very high spatial resolution, good sensitivity, and a large field-of-view allowing the examination of more than one animal in a single scan or a whole body scan of larger species in a single bed position. Excellent image quality has been obtained through list-mode-based EM reconstruction using resolution recovery. However, quantitative results on local uptake are still missing due to both (1) lack of energy discrimination and (2) inaccurate characterization of random events recorded by the scanner. In this work we describe how quantification can be achieved through the use of an appropriate Monte Carlo simulation of the quadHIDAC. The complex structure of the quadHIDAC has been completely implemented in a Geant4 simulation. Point sources, line sources, cylindrical phantoms, and voxelized image data have been successfully simulated and compared to real measurements. The magnitude and spatial distribution of scattered and random events could be quantitatively characterized for the different phantom geometries. The simulation provides access to information on single hit distributions resulting in appropriate randoms corrections in image reconstruction. Both randoms and scatter correction is demonstrated to improve quantification. Their accuracy and performance was tested on simulated and measured data. Using simulation-based correction techniques for quantitative image reconstruction, multi-wire proportional chamber-based PET technology may be attractive for future high resolution PET scanners.
In Plant Activation: An Inducible, Hyperexpression Platform for Recombinant Protein Production in Plants[W][OPEN]

This work describes a novel platform for recombinant protein production that is essentially transient expression from a stably transformed plant. The system provides both activation and amplification of transgene expression in planta and in this study was exemplified using both a therapeutic and industrial protein. The platform is not host limited and can be adapted to large-scale production. In this study, we describe a novel protein production platform that provides both activation and amplification of transgene expression in planta. The In Plant Activation (INPACT) system is based on the replication machinery of tobacco yellow dwarf mastrevirus (TYDV) and is essentially transient gene expression from a stably transformed plant, thus combining the advantages of both means of expression. The INPACT cassette is uniquely arranged such that the gene of interest is split and only reconstituted in the presence of the TYDV-encoded Rep/RepA proteins. Rep/RepA expression is placed under the control of the AlcA:AlcR gene switch, which is responsive to trace levels of ethanol. Transgenic tobacco (Nicotiana tabacum cv Samsun) plants containing an INPACT cassette encoding the β-glucuronidase (GUS) reporter had negligible background expression but accumulated very high GUS levels (up to 10% total soluble protein) throughout the plant, within 3 d of a 1% ethanol application. The GUS reporter was replaced with a gene encoding a lethal ribonuclease, barnase, demonstrating that the INPACT system provides exquisite control of transgene expression and can be adapted to potentially toxic or inhibitory compounds. The INPACT gene expression platform is scalable, not host-limited, and has been used to express both a therapeutic and an industrial protein.
The Length, Phosphorylation State, and Primary Structure of the RNA Polymerase II Carboxyl-terminal Domain Dictate Interactions with mRNA Capping Enzymes*

The carboxyl-terminal domain (CTD) of elongating RNA polymerase II serves as a landing pad for macromolecular assemblies that regulate mRNA synthesis and processing. The capping apparatus is the first of the assemblies to act on the nascent pre-mRNA and the one for which binding of the catalytic components is most clearly dependent on CTD phosphorylation. The present study highlights a distinctive strategy of cap targeting in fission yeast whereby the triphosphatase (Pct1) and guanylyltransferase (Pce1) enzymes of the capping apparatus do not interact physically with each other (as they do in budding yeast and metazoans), but instead bind independently to the phosphorylated CTD. In vivointeractions of Pct1 and Pce1 with the CTD in a two-hybrid assay require 12 and 14 tandem repeats of the CTD heptapeptide, respectively. Pct1 and Pce1 bind in vitro to synthetic CTD peptides containing phosphoserine uniquely at position 5 or doubly at positions 2 and 5 of each of four tandem YSPTSPS repeats, but they bind weakly (Pce1) or not at all (Pct1) to a peptide containing phosphoserine at position 2. These results illustrate how remodeling of the CTD phosphorylation array might influence the recruitment and dissociation of the capping enzymes during elongation. But how does the CTD structure itself dictate interactions with the RNA processing enzymes independent of the phosphorylation state? Using CTD-Ser5 phosphopeptides containing alanine substitutions at other positions of the heptad, we define essential roles for Tyr-1 and Pro-3 (but not Thr-4 or Pro-6) in the binding ofSchizosaccharomyces pombeguanylyltransferase. Tyr-1 is also essential for binding and allosteric activation of mammalian guanylyltransferase by CTD Ser5-PO4, whereas alanine mutations of Pro-3 and Pro-6 reduce the affinity for the allosteric CTD-binding site. These are the first structure-activity relationships deduced for an effector function of the phosphorylated CTD.
Resistance to nodulation of cv. Afghanistan peas is overcome by nodX, which mediates an O‐acetylation of the Rhizobium leguminosarum lipo‐oligosaccharide nodulation factor

Only some strains of Rhizobium leguminosarum biovar viciae can efficiently nodulate varieties of peas such as cv. Afghanistan, which carry a recessive allele that blocks efficient nodulation by most western isolates of R. I. viciae. One strain (TOM) which can nodulate cv. Afghanistan peas has a gene (nodX) that is required to overcome the nodulation resistance. Strain TOM makes significantly lower amounts of lipo‐oligosaccharide nodulation factors than other strains of R. I. viciae. and this effect appears to be due to lower levels of nod gene induction. These nodulation factors are similar to those from other R. I. viciae. strains in that they consist of an oligomer of four or five β1‐4‐linked N‐acetylglucosamine residues in which the terminal non‐reducing glucosamine carries an O‐acetyl group and a C18:4 or C18:1N‐acyl group. However, one of the nodulation factors made by strain TOM differs from the factors made by other strains of R. I. viciae. in that it carries an O‐acetyl group on the C‐6 of the reducing N‐acetylglucosamine residue. This acetylation is NodX‐dependent and the pentameric nodulation factor is acetylated on the reducing N‐acetylglucosamine residue whereas the tetrameric nodulation factor is not. Although the nodL gene product is also an O‐acetyl transferase (it O‐acetylates the C‐6 of the terminal non‐reducing glucosamine), there is very little similarity between the amino acid sequences of these two acetyl transferases.
Depiction of indigenous food in translated isiXhosa folk narratives and biographies

The lack of translational and terminological resources for the South African translator who translates from English into an African language has been described by researchers in the field as the biggest challenge that translators have to deal with daily. But no attention has been paid to the scarcity of English equivalents for indigenous culture-specific terms in translated texts and English original writings based on African culture. As food is an ingredient of one’s culture, this article examines the strategies used in describing indigenous Xhosa food in translated folk narratives and in extracts from autobiographies/biographies of three prominent Xhosa figures, i.e. Magona, Mankazana and Mandela. The theoretical framework applied in this research is Descriptive Translation Studies (DTS). Theorists in this field do not prescribe how translations ought to be done but describe how they have been done. DTS takes into consideration the political, social, cultural and literary norms and conventions that influence the translation process. This approach has been chosen because the research concerns the rendition of a cultural aspect, namely, food.
Variable restriction endonuclease sites of herpes simplex virus type 1 isolates from encephalitic, facial and genital lesions and ganglia.

The distribution of restriction endonuclease (RE) sites was compared for 84 herpes simplex virus type 1 (HSV-1) isolates obtained from the ganglia, facial lesions, genital lesions and from brain tissue from herpes encephalitis cases. The isolates came from Canada, the U.K., the U.S.A. and Japan. Out of a total of 224 sites identified, 87 were variable. Three of the 30 most variable sites were at significantly (P less than 0.05) different frequencies in groups of isolates from distinct anatomical sites of isolation; one of these, and a further two sites, were at significantly different frequencies in groups from distinct geographical origins. There are at least two inter-related linkage groups. However, most of the site combinations appear to be random. The variability of RE sites in contiguous genome segments, which include both non-coding and coding sequences, show a marked heterogeneity, indicating that some viral gene sequences are more variable than others. The three RE sites at different frequencies in viral groups from distinct anatomical sites of isolation are in two genome segments: map units 27 to 35 and 50 to 57. We infer from the observed associations with anatomical site of viral isolation that part of at least one of these segments may modulate viral virulence in man following infection.
Smad3 as a mediator of the fibrotic response

Transforming growth factor‐β (TGF‐β) plays a central role in fibrosis, contributing to the influx and activation of inflammatory cells, the epithelial to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts and their subsequent elaboration of extracellular matrix. TGF‐β signals through transmembrane receptor serine/threonine kinases to activate novel signalling intermediates called Smad proteins, which modulate the transcription of target genes. The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF‐β/activin, shows that most of the pro‐fibrotic activities of TGF‐β are mediated by Smad3. Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF‐β and do not autoinduce TGF‐β. The loss of Smad3 also interferes with TGF‐β‐mediated induction of EMT and genes for collagens, plasminogen activator inhibitor‐1 and the tissue inhibitor of metalloprotease‐1. Smad3 null mice are resistant to radiation‐induced cutaneous fibrosis, bleomycin‐induced pulmonary fibrosis, carbon tetrachloride‐induced hepatic fibrosis as well as glomerular fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic conditions that are induced by EMT, such as proliferative vitreoretinopathy, ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation‐induced fibrosis. Small moleucule inhibitors of Smad3 may have tremendous clinical potential in the treatment of pathological fibrotic diseases.
Feasibility of a Website and a Hospital-Based Online Portal for Young Adults With Juvenile Idiopathic Arthritis: Views and Experiences of Patients

Background To improve knowledge and to encourage active involvement of young adults with juvenile idiopathic arthritis (JIA), an informative website with written and video information and an online portal with access to the personal medical record, self-monitoring, and e-consult functionalities were developed. Before implementing these applications in daily practice, it is important to gain insight into their feasibility in terms of ease of use, perceived usefulness and intention to use. Objective The aim of this study was to evaluate and to examine the feasibility of the website and the online portal for young adults with JIA. Methods A qualitative, feasibility study was conducted among the first users: 13 young adults with JIA. After provided access to the website and online portal, patients were interviewed on perceived usefulness, ease of use, and intention to (re)use the applications. Results Participants in the study considered the website and online portal as useful and easy-to-use. New medical information and feedback would motivate them to revisit the applications again. On the website, videos showing other young adults, telling how they handle their condition, were found as the most useful. On the portal, access to their medical records was most appreciated: it made the young JIA patients feel in control and it helped them monitor symptoms and disease activity. e-consults were thought to facilitate communication with physicians. Conclusions The young adults considered both the website and the online portal as feasible, but they also had valuable suggestions to improve accessibility and use. Based on these findings, a news and event section was added on the website and a direct link was made to a discussion board and social media. To provide and support health information, the website is actively used in daily care. Considering the online portal, the use of self-monitoring tools and e-consult can be stimulated if there is direct linkage to treatment and feedback from the multidisciplinary team. Feasibility testing, before implementing the website and online portal in daily practice, has proven to be a valuable step. Results led to improvements in terms of integration into standard care and topics for further research.
Divergence of developmental trajectories is triggered interactively by early social and ecological experience in a cooperative breeder

Significance Cooperative breeding represents the pinnacle of vertebrate social evolution. Helpers in cooperatively breeding species are characterized by a life-long potential to reproduce. Therefore it has been predicted that cooperative breeders lack an early specialization into subordinate helpers and dominant breeders. In a 3-year life-history experiment, we manipulated the social and ecological environments jointly during the early postnatal period of a cooperatively breeding vertebrate, the “Princess cichlid” Neolamprologus pulcher. We found that individuals did specialize in distinct behavioral competences, which led to either delayed dispersal or early independent breeding. The divergence into different behavioral trajectories became apparent only by manipulating both early social and ecological experiences, highlighting the importance of multivariate influences on the development of social trajectories. Cooperative breeders feature the highest level of social complexity among vertebrates. Environmental constraints foster the evolution of this form of social organization, selecting for both well-developed social and ecological competences. Cooperative breeders pursue one of two alternative social trajectories: delaying reproduction to care for the offspring of dominant breeders or dispersing early to breed independently. It is yet unclear which ecological and social triggers determine the choice between these alternatives and whether diverging developmental trajectories exist in cooperative vertebrates predisposing them to dispersal or philopatry. Here we experimentally reared juveniles of cooperatively breeding cichlid fish by varying the social environment and simulated predation threat in a two-by-two factorial long-term experiment. First, we show that individuals develop specialized behavioral competences, originating already in the early postnatal phase. Second, these specializations predisposed individuals to pursue different developmental trajectories and either to disperse early or to extend philopatry in adulthood. Thus, our results contrast with the proposition that social specializations in early ontogeny should be restricted to eusocial species. Importantly, social and ecological triggers were both required for the generation of divergent life histories. Our results thus confirm recent predictions from theoretical models that organisms should combine relevant information from different environmental cues to develop integrated phenotypes.
The intratumoral distribution of nuclear β‐catenin is a prognostic marker in colon cancer

Most colon cancers harbor mutations of APC or β‐catenin, both of which may lead to nuclear β‐catenin accumulation in the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear β‐catenin accumulation is heterogeneous throughout the tumor and often confined to the tumor margin. Herein, the authors investigated whether the intratumoral distribution of nuclear β‐catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients.
Legal fundamentals of surrogate decision making.

The four previous articles in this series have traced the history of patient autonomy and have identified its ethical and legal foundations. Patient autonomy is highly valued in the United States to the extent that the patient does not lose the right of self-determination when he or she loses the capacity to make health-care decisions for him or herself. The law has devised several tools to promote "prospective autonomy. " One mechanism is the instructional advance directive or living will. But most of us do not write such directives. Another mechanism is the proxy directive or durable power of attorney for health care, designating another person, a surrogate, to direct the course of our medical treatment upon our incapacity. But most of us do not do that either. Therefore, the most common mechanism by which our prospective autonomy is protected and promoted is through the informal selection of surrogates based on statutory priority lists. These "default" surrogates are the most numerous type of surrogate. This article explains the importance and legal fundamentals of surrogate decision making. It first describes five basic types of surrogates. The article then looks at the role of these surrogates and how they are supposed to make decisions on the patient's behalf. Unfortunately, surrogate performance is often mediocre or poor. There are significant and persistent obstacles to good surrogate decision making. After explaining these problems, the article concludes by identifying several solutions.
Hemoglobin variants, hematological parameters and β-globin gene cluster haplotypes in an isolated Amerindian group from the Orinoco River Delta

Background: Several previous studies reported that the Venezuelan Warao Indians presented unusual genetic characteristics. Aim: The present study checked previous reports of a high frequency of hereditary persistence of fetal hemoglobin (HPFH) and examined other hematological traits. Subjects and methods: Standard hematology, electrophoresis on cellulose acetate, fetal hemoglobin alkali denaturation, γ-globin chain, DNA amplification and sequencing, and denaturing gradient gel electrophoresis determinations were performed in 269 individuals living in two localities of the Orinoco River Delta. Results: Two βs genes, in apparently non-related individuals, were found. HPFH, detected in this same population of Warao Indians 25 years ago, was present in heterozygous form in five individuals from a large kindred, with hemoglobin F levels ranging from 3.7% to 8%, and with a pancellular distribution. The HPFH mutation was of the deletional type. β-globin gene haplotypes were determined by direct counting (through family studies) in 150 chromosomes; 26% of the 150 examined cluster presented haplotype 2, 22% haplotype 6, and 13% a new, Warao haplotype. Haplotype 3, of probable African origin, was also found with a frequency of 5%. Conclusions: The presence of the HPFH mutation was confirmed, and the new β-globin gene haplotype together with the presence of other rare variants indicates that the Warao are very distinctive in relation to other Native Americans. Evidence was also found of a slight admixture from Africa-derived subjects (Layrisse et al. 1988).