Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables.
cis-Acting Determinants of 7SL RNA Packaging by HIV-1

ABSTRACT The host noncoding RNA 7SL is highly enriched in the virions of retroviruses. We examined the regions of 7SL that mediate packaging by HIV-1. Both the Alu domain and the S domain were sufficient to mediate specific packaging when expressed separately as truncations of 7SL. However, while the Alu domain competed with endogenous 7SL for packaging in proportion to Gag, the S domain was packaged additively, implying that the Alu and S domains are packaged via separate mechanisms and that the Alu domain is packaged by the same mechanism as endogenous 7SL. Further truncations of the Alu domain or mutation of the Alu domain helix 5c region significantly reduced packaging efficiency, implicating helix 5c as critical for packaging, reinforcing the finding that 7SL packaging is highly selective, and confirming that 7SL is not passively acquired. Surprisingly, when the Alu domain was mutated so that it no longer contained a binding site for the SRP protein heterodimer SRP9/14, it was no longer packaged in a competitive manner but instead was packaged additively with endogenous 7SL. These data support a model in which 7SL RNA is packaged via interactions between Gag and a 7SL RNA structure that exists transiently at a discrete stage of SRP biogenesis. Our data further indicate that a secondary “additive” pathway exists that can result in the packaging of certain 7SL derivatives in molar excess to endogenously packaged 7SL.
Comparative Analysis of the Capacity of Elite Suppressor CD4+ and CD8+ T Cells To Inhibit HIV-1 Replication in Monocyte-Derived Macrophages

ABSTRACT Elite controllers or suppressors (ESs) are HIV-1-infected individuals who are able to maintain viral loads below the limit of detection of clinical assays without antiretroviral therapy. The mechanisms of virologic control are not fully understood, but ESs have been shown to have a more effective CD8+ T cell response to infected CD4+ T cells than chronic progressors (CPs). While macrophages are another cell type productively infected by HIV-1, few studies have examined the ability of primary effector T cells to suppress HIV-1 replication in these target cells. Here, we compared the ability of unstimulated primary CD4+ and CD8+ effector T cells to suppress viral replication in monocyte-derived macrophages (MDMs) in ESs and CPs. While CD4+ effector T cells were capable of inhibiting viral replication in MDMs, the magnitude of this response was not significantly different between ESs and CPs. In contrast, the CD8+ T cells from ESs were significantly more effective than those from CPs at inhibiting viral replication in MDMs. The CD4+ T cell response was partially mediated by soluble factors, while the CD8+ T cell response required cell-to-cell interaction. Our results suggest that the individual contributions of various effector cells should be considered in rational vaccine design and in ongoing eradication efforts. IMPORTANCE Elite suppressors are individuals capable of maintaining low-level viremia in HIV-1 infection without antiretroviral drugs. Their T cell responses have been implicated in eliminating infected CD4+ T cells, and as such, elite suppressors may represent a model of a functional cure of HIV-1 infection. Here, we sought to determine whether the suppressive T cell responses against infected CD4+ T cells also apply to infected macrophages by comparing the responses of elite suppressors and HIV-1-positive individuals on highly active antiretroviral therapy (HAART). Our results show that the CD8+ cells but not CD4+ T cells from elite suppressors have a response against infected macrophages superior to the response of CD8+ cells from patients on HAART. Our results suggest that the induction of a CD8+ T cell response effective against infected macrophages is an outcome to consider in rational vaccine design.
Ontology-Based Information Extraction from Handwritten Documents

In this paper we introduce a new layer for the task of handwriting recognition. We add semantic information by means of ontologies. The task of our recognizer therefore is not only to recognize the ASCII transcription of the handwritten document, but also to identify the semantic concepts which appear in the text. This task is called ontology-based information extraction (OBIE), which has been applied to electronic documents recently. OBIE methods first segment the text into tokens, then identify their values and their corresponding instances of the ontology, and finally try to generate new facts based on the text. To the authors’ knowledge, in this paper OBIE is proposed for the first time in handwriting literature. In our experiments we have evaluated the process up to the instantiation. We have found that using not only the top alternative, but also the k-best alternatives increases the performance of information extraction. Furthermore, the use of an ontology-based lexicon results in another performance increase.
Farsi/Arabic Handwritten from Machine-Printed Words Discrimination

Separating handwritten texts from machine-printed materials is a desirable task towards a general document analysis system. In this paper, we proposed a simple and effective method to discriminate handwritten from machine-printed words in Farsi/Arabic documents. After finding word blocks, three different feature sets were extracted. They include two well-established features, previously used for Latin handwritten from machine-printed text separation, and a new feature, called baseline profile. Then, extracted features were combined together to obtain a feature vector with 34 elements. SVM and KNN classifiers were utilized to separate handwritten and machine-printed words. To evaluate the proposed method, some special forms, designed for word separation, were used. Experimental results show that our system differentiates between handwritten and machine-printed words with the overall accuracy of 97.1%.
Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types

ABSTRACT The herpes simplex virus 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase that promotes the degradation of several host cell proteins. Most studies have found that ICP0 promotes the loss of IFI16 in infected cells, but one study reported that ICP0 was not necessary or sufficient for loss of IFI16 in a tumor-derived cell line. Therefore, in this study, we examined the requirement for ICP0 in promoting the loss of IFI16 in several normal and tumor-derived cell lines. HSV-1 infection resulted in an observable decrease of IFI16 protein levels in normal human foreskin fibroblasts (HFFs), normal oral keratinocytes (NOKs), and HeLa cells but not in U2OS cells. During infection with an ICP0-null virus, we observed a reduced loss of IFI16 in HFFs and NOKs but not in HeLa cells. Ectopic expression of ICP0 from a transfected plasmid was sufficient to promote the loss of IFI16 in HFFs and NOKs. In the absence of ICP0, we observed a delayed reduction of IFI16 protein that correlated with a reduction in the steady-state levels of IFI16 mRNA. In addition, we show that the ICP0-independent loss of IFI16 in HeLa cells is dependent in part on the activity of the viral virion host shutoff (vhs) tegument protein. Together, these results demonstrate that HSV-1 promotes the loss of IFI16 through at least two mechanisms: (i) by ICP0-dependent degradation of IFI16 and (ii) by vhs-dependent turnover of IFI16 mRNA. In addition, this study highlights a potential intrinsic difference between normal and tumor-derived cells for the activities of IFI16 and HSV-1 ICP0. IMPORTANCE HSV-1 is a ubiquitous virus that establishes a lifetime persistent infection in humans. The relative success of HSV-1 as a pathogen is, in part, dependent on the expression of viral proteins that counteract host intrinsic defense mechanisms and that modulate immune responses during viral infection. In this study, we examined the relative roles of two viral gene products for the ability to promote loss of the antiviral IFI16 DNA sensor. We demonstrate that the viral immediate early ICP0 protein plays a dominant role in the loss of IFI16 in normal, but not tumor-derived, human cell lines. In contrast, viral vhs-mediated loss of IFI16 by mRNA destabilization is revealed to be dominant in tumor-derived cells in which ICP0 is nonfunctional. Together, these results contribute to our understanding of how HSV-1 modulates IFI16 protein levels and highlight cell-type-dependent differences between normal and tumor-derived cells.
Pain experience and expectations of physiotherapy from a cultural perspective

The purpose of the present study was to investigate and compare pain experience and expectations of physiotherapy among patients with chronic pain coming from different cultures. In total, 74 subjects from Sweden, Iran and Iraq participated, with equal numbers in each group. Pain was assessed by the McGill Pain Questionnaire Short Form and by the Margolis pain drawing and scoring system. One-way ANOVAs showed that the groups differed significantly in sensory (p<0.001) and affective (p<0.001) pain, and in pain intensity (p<0.01). Tukey's HSD post hoc tests showed that subjects from Iran and Iraq reported significantly higher levels of sensory and affective pain as well as pain intensity than the Swedish subjects did. No difference between the groups was found in pain distribution. Regarding expectations of physiotherapy, the Swedish group had larger confidence than the Iran group and especially the Iraq group in physiotherapy as a treatment and as a method of improvement. Another difference between the groups was that subjects from Iraq considered rest a good treatment towards their problems more than subjects from the other two groups did. The results support earlier studies that conclude there are cultural differences in pain experience.
Clinical Coder Training Initiatives in Ireland

The Hospital In-Patient Enquiry and National Perinatal Reporting System (HIPE & NPRS) Unit of the Economic and Social Research Institute in Ireland requested a review of its coder training programs and data quality initiatives, primarily because of the decision to implement a major change in Ireland's morbidity classification in January 2005. In August 2004, a formative evaluation using qualitative methods was conducted to assess the Unit's programs and initiatives. A number of opportunities for building on the solid frameworks the Unit has implemented were identified. In this paper, we focus on the Unit's coder training programs. The Unit's data quality initiatives will be discussed in a subsequent paper (Bramley & Reid 2005).
Does the Electronic Patient Record Support the Discharge Process? A Study on Physicians' Use of Clinical Information Systems during Discharge of Patients with Coronary Heart Disease

This study has been performed in order to categorise and measure usage of different information sources and types in a well defined stage of clinical work. The underlying motivation is to improve computer-supported presentation and retrieval of relevant information and to be able to evaluate the functionality of a future improved interface to the electronic patient record (EPR). By observing 52 discharge processes and categorising information types and sources, we have observed that the paper chart is used as a primary source of information about recent events and procedures, while the EPR is mostly used for retrieving background information and verification. Direct communication with other clinicians and the patient is also important during the discharge process. Results from an additional survey show that the physicians report greater use of the EPR than the result from the observational study. The study clearly indicates that there is a large potential for improved EPR systems that support the physicians in their work regarding discharge of patients, especially in the future planning part of the discharge.
Growth Determinants for H5N1 Influenza Vaccine Seed Viruses in MDCK Cells

ABSTRACT H5N1 influenza A viruses are exacting a growing human toll, with more than 240 fatal cases to date. In the event of an influenza pandemic caused by these viruses, embryonated chicken eggs, which are the approved substrate for human inactivated-vaccine production, will likely be in short supply because chickens will be killed by these viruses or culled to limit the worldwide spread of the infection. The Madin-Darby canine kidney (MDCK) cell line is a promising alternative candidate substrate because it supports efficient growth of influenza viruses compared to other cell lines. Here, we addressed the molecular determinants for growth of an H5N1 vaccine seed virus in MDCK cells, revealing the critical responsibility of the Tyr residue at position 360 of PB2, the considerable requirement for functional balance between hemagglutinin (HA) and neuraminidase (NA), and the partial responsibility of the Glu residue at position 55 of NS1. Based on these findings, we produced a PR8/H5N1 reassortant, optimized for this cell line, that derives all of its genes for its internal proteins from the PR8(UW) strain except for the NS gene, which derives from the PR8(Cambridge) strain; its N1 NA gene, which has a long stalk and derives from an early H5N1 strain; and its HA gene, which has an avirulent-type cleavage site sequence and is derived from a circulating H5N1 virus. Our findings demonstrate the importance and feasibility of a cell culture-based approach to producing seed viruses for inactivated H5N1 vaccines that grow robustly and in a timely, cost-efficient manner as an alternative to egg-based vaccine production.
Respiratory Syncytial Virus Grown in Vero Cells Contains a Truncated Attachment Protein That Alters Its Infectivity and Dependence on Glycosaminoglycans

ABSTRACT Human respiratory syncytial virus (RSV) contains a heavily glycosylated 90-kDa attachment glycoprotein (G). Infection of HEp-2 and Vero cells in culture depends largely on virion G protein binding to cell surface glycosaminoglycans (GAGs). This GAG-dependent phenotype has been described for RSV grown in HEp-2 cells, but we have found that it is greatly reduced by a single passage in Vero cells. Virions produced from Vero cells primarily display a 55-kDa G glycoprotein. This smaller G protein represents a post-Golgi compartment form that is lacking its C terminus, indicating that the C terminus is required for GAG dependency. Vero cell-grown virus infected primary well-differentiated human airway epithelial (HAE) cell cultures 600-fold less efficiently than did HEp-2 cell-grown virus, indicating that the C terminus of the G protein is also required for virus attachment to this model of the in vivo target cells. This reduced infectivity for HAE cell cultures is not likely to be due to the loss of GAG attachment since heparan sulfate, the primary GAG used by RSV for attachment to HEp-2 cells, is not detectable at the apical surface of HAE cell cultures where RSV enters. Growing RSV stocks in Vero cells could dramatically reduce the initial infection of the respiratory tract in animal models or in volunteers receiving attenuated virus vaccines, thereby reducing the efficiency of infection or the efficacy of the vaccine.
Virus Particle Release from Glycosphingolipid-Enriched Microdomains Is Essential for Dendritic Cell-Mediated Capture and Transfer of HIV-1 and Henipavirus

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DCs) to promote its transmission to T cells. We recently reported that the capture of HIV-1 by mature dendritic cells (MDCs) is mediated by an interaction between the glycosphingolipid (GSL) GM3 on virus particles and CD169/Siglec-1 on MDCs. Since HIV-1 preferentially buds from GSL-enriched lipid microdomains on the plasma membrane, we hypothesized that the virus assembly and budding site determines the ability of HIV-1 to interact with MDCs. In support of this hypothesis, mutations in the N-terminal basic domain (29/31KE) or deletion of the membrane-targeting domain of the HIV-1 matrix (MA) protein that altered the virus assembly and budding site to CD63+/Lamp-1-positive intracellular compartments resulted in lower levels of virion incorporation of GM3 and attenuation of virus capture by MDCs. Furthermore, MDC-mediated capture and transmission of MA mutant viruses to T cells were decreased, suggesting that HIV-1 acquires GSLs via budding from the plasma membrane to access the MDC-dependent trans infection pathway. Interestingly, MDC-mediated capture of Nipah and Hendra virus (recently emerged zoonotic paramyxoviruses) M (matrix) protein-derived virus-like particles that bud from GSL-enriched plasma membrane microdomains was also dependent on interactions between virion-incorporated GSLs and CD169. Moreover, capture and transfer of Nipah virus envelope glycoprotein-pseudotyped lentivirus particles by MDCs were severely attenuated upon depletion of GSLs from virus particles. These results suggest that GSL incorporation into virions is critical for the interaction of diverse enveloped RNA viruses with DCs and that the GSL-CD169 recognition nexus might be a conserved viral mechanism of parasitization of DC functions for systemic virus dissemination. IMPORTANCE Dendritic cells (DCs) can capture HIV-1 particles and transfer captured virus particles to T cells without establishing productive infection in DCs, a mechanism of HIV-1 trans infection. We have recently identified CD169-mediated recognition of GM3, a host-derived glycosphingolipid (GSL) incorporated into the virus particle membrane, as the receptor and ligand for the DC-HIV trans infection pathway. In this study, we have identified the matrix (MA) domain of Gag to be the viral determinant that governs incorporation of GM3 into HIV-1 particles, a previously unappreciated function of the HIV-1 MA. In addition, we demonstrate that the GSL-CD169-dependent trans infection pathway is also utilized as a dissemination mechanism by henipaviruses. GSL incorporation in henipaviruses was also dependent on the viral capsid (M) protein-directed assembly and budding from GSL-enriched lipid microdomains. These findings provide evidence of a conserved mechanism of retrovirus and henipavirus parasitization of cell-to-cell recognition pathways for systemic virus dissemination.
High q-factor distributed bragg reflector resonators with reflectors of arbitrary thickness

The Bragg reflection technique improves the Q-factor of a resonator by reducing conductor and dielectric losses. This is achieved by designing a low-loss inner resonant region (usually free space) surrounded by an outer anti-resonant region made of distributed Bragg reflector layers. In this paper we develop a simple non-Maxwellian model and apply it to design three distinct cylindrical Bragg resonators based on the same set of single-crystal sapphire plates and rings by changing only the dimension of the cavity that supports the structure. To accomplish this, the simple model allows an arbitrary thickness for either the horizontal or the cylindrical dielectric reflectors by relaxing the condition that they must be lambda4 thick. The model also allows for higher-order field variations in both the resonant and the anti-resonant regions. The resonators were constructed and experimental results were compared with the simple model and the rigorous method of lines analysis. For the fundamental mode, an unloaded Q-factor of 234,000 at 9.7 GHz was obtained. This is larger than that for a whispering gallery mode resonator. The resonator also exhibited a greatly reduced spurious mode density when compared to an overmoded whispering gallery mode resonator.
Uterine Motility in the Cow During Puerperium

Summary The objective of the study was to determine uterine motility during the postpartum period in cattle. In the present study spontaneous uterine activity was recorded during postpartum period using electrodes which were surgically implanted into the myometrium 4-6 weeks before parturition. After the placenta has been released 4-8 hours post part, spontaneous uterine motility drastically decreased until the second week post part. The effects of oxytocin, depotocin, prostaglandin, ergometrin, detomidin on the uterine contractility, during postpartum period were investigated. Oxytocin and carbotocin given intravenously always provoked strong uterine contractions. Prostaglandin F2alpha and detomidinum HC1 stimulated uterine activity in the early puerperium. Following administration of ergometrin unequal response was recorded. Ultrasonographic examinations were performed daily with real time B-mode scanner equipped with a 5.0 MHz linear-array transducer (Aloka 210, Pie Medical). 10 muciparous Black-White-Holstein cows between 2 and 4 years old and 550-650 kg b.w. were used. A 6-min scan of the longitudinal view of the uterine body was recorded using video cassette recorder connected to the ultrasound scanner. A scoring system was used to determines uterine motility. Contractility scores were higher just after parturition then in the following times. Blood samples were collected daily from jugular vein for plasma progesterone and estrogen concentrations. Changes in uterine activity were associated with plasma progesterone and estrogen level.
The natural history of eating pathology in attenders to primary medical care

Sixty-nine subjects with abnormal eating attitudes ascertained from an epidemiological study in family practice were followed-up for a period of up to 30 months. There was little clinical change in patients with the full syndrome of bulimia nervosa or with partial syndromes. Subjects who were dieting obsessionally at entry to the study appeared to have a definite potential to develop more severe syndromes. Early intervention to prevent the development of chronic dieting may be important in the prevention of eating disorders.