Miracle-dz/UniFAR-FTUs huggingface dataset:
RANK as a therapeutic target in cancer

The RANK signaling pathway has emerged as a new target in breast cancer as receptor activator of nuclear factor κB ligand (RANKL) and its receptor RANK mediate the pro‐tumorigenic role of progesterone in the mammary gland. Thousands of cancer patients worldwide are already taking RANKL inhibitors for the management of bone metastasis, given the relevance of this pathway in osteoclastogenesis and bone resorption. RANK signaling also has multiple divergent effects in immunity and inflammation, both in the generation of active immune responses and in the induction of tolerance: it is required for lymph node organogenesis, thymic medullary epithelial development and self‐tolerance, and regulates activation of several immune cells and inflammatory processes. The RANK pathway interferes with mammary epithelial differentiation and mediates the major proliferative response of mammary epithelium to progesterone and progesterone‐driven expansion of mammary stem cells; it also controls hair follicle and epidermal stem cell homeostasis, pointing to RANK as a key regulator of epithelial stemness. Here we revisit the main functions of RANK signaling in bone remodeling, immune cells and epithelial differentiation. We also discuss the mechanistic evidence that supports its pleiotropic effects on cancer: from bone metastasis to immune and cancer‐cell‐dependent effects.
Healthcare law in France: towards healthcare emancipation for minors

In France, since 1974 the rights of minors have been gaining ground. The first provisions to this end concerned medical acts in relation to the minor's sexuality (contraceptives and pregnancy termination). The law dated March 4, 2002, relating to patients' rights, gave more scope to this movement, by widening minors' rights so that they could demand confidentiality with regard to their parents. The minor's exercising of these rights can pose a lot of problems. In French law, parental authority is the main representation of the minor. The medical doctor treating a minor must obtain parental authorization. However, the public healthcare code provides that the doctor can override parental wishes during some situations (emergency; parents refuse). But these situations are exceptional. Since 2002, the legislator has gone further, by allowing the doctor to grant requests for care by the minor without parental authorization. However, parental authority remains the normal framework for the protection of a minor. The doctor will have to judge the reasoning and motives of a minor requesting confidentiality regarding their parents in order to decide whether he should grant or refuse care in such conditions.
Role of “perceived risks” in adopting mobile government (m-government) services in India

Purpose This paper aims to investigate the role of “perceived risks” in adopting mobile government (m-government) services in India. Design/methodology/approach Conceding that “privacy risks” are one of the major factors that influence the adoption of e-services, the impact of “perceived risks” alongside “social efficacy,” “influence” of significant others and “attitude” on the adoption of m-government services in India has been underlined here. Specifically, the study has been conducted with 311 actual m-government users and constructs have been derived from existing theories like Technology Acceptance Model (TAM), Unified Theory of Acceptance and Use of Technology (UTAUT) and Theory of Planned Behavior (TPB). Multiple regression analysis has been conducted to analyze the data focused on constructs as: Perceived Risks (PR), Influence (I), Self-efficacy (SE), Attitude (ATT) and Behavioral Intention to Adopt m-government services (BI). Findings Results show that while the respondents perceive that adoption of m-government services is risk-free and safe, there is no impact of the interpersonal relationships on m-government adoption. There is more inclination to adopt m-government services conceding that the respondents perceive that they have the self-efficacy to operate such services. M-government services are being tapped regularly by the respondents and there is more inclination to adopt m-government services among the public sector employees and self-employed respondents in comparison with the ones who are students or unemployed. In terms of age, those in the age group of 31–50 are more inclined to adopt m-government services in comparison with the rest. Originality/value Exploration of “perceived risks” and other factors has been less in the context of m-government studies. The present study fills the gap in two ways: first, it undertakes the investigation in a developing country conceding that empirical studies on m-government adoption are few in Indian context, and second, it throws light on the role of “adoption” of m-government services in contrast with the “use” of e-government services.
An Early Regulatory Function Required in a Cell Type-Dependent Manner Is Expressed by the Genomic but Not the cDNA Copy of the Herpes Simplex Virus 1 Gene Encoding Infected Cell Protein 0

ABSTRACT The α0 genes of herpes simplex virus 1 (HSV-1) contain three exons. Earlier studies have shown that the substitution of genomic sequences with a cDNA copy does not alter the capacity of the virus to replicate or establish latent infection. Other studies have demonstrated that HSV-1 may express alternatively spliced forms of α0 transcripts. The studies reported here centered on a mutant HSV-1(vCPc0) strain in which the genomic copies of the α0 gene were replaced with cDNA copies. From our research, we report the following observations. (i) In contrast to events transpiring in cells infected with wild-type virus, the expression of HSV-1(vCPc0) genes was delayed or restricted to α genes for many hours in rabbit skin cells and to a lesser extent in HEp-2 cells but not in Vero cells. This delay in the expression of HSV-1(vCPc0) β or γ genes was also multiplicity of infection dependent. (ii) Exposure to MG132, a proteasomal inhibitor, before infection with wild-type virus had no significant effect on the accumulation of viral proteins in Vero cells and caused an only slight delay in viral gene expression in rabbit skin cells in a multiplicity of infection-dependent fashion. The drug had no effect when it was added to the medium 3 h after infection. (iii) Rabbit skin or HEp-2 cells exposed to MG132 3 h after infection with the HSV-1(vCPc0) mutant accumulated only α proteins. This restriction was cell type dependent but not multiplicity of infection dependent. (iv) Both the delay in the expression of β and γ genes and the effect of MG132 added to the medium 3 h after infection were rescued by restoration of the intron 1 sequences in the HSV-1(vCPc0) mutant. However, cells transduced by baculoviruses expressing intron 1 RNA did not complement the HSV-1(vCPc0) mutant, suggesting that the function of intron 1 is in cis rather than in trans. We came to the following conclusions as a result. (i) Post-α gene expression requires the involvement of the proteasomal pathway in a cell type-dependent manner. Consistent with this requirement, the proapoptotic functions of MG132 are blocked in cells infected before exposure to the drug but not after exposure. (ii) A function encoded by the α0 gene that is absent from the cDNA copy is required for viral gene expression in a cell type- and multiplicity of infection-dependent fashion. The absence of this master function delays but does not ultimately block viral gene expression in the cell lines tested here.
Screening for Diabetic Cardiac Autonomic Neuropathy Using a New Handheld Device

Background: Cardiac autonomic neuropathy (CAN) is a serious complication of longstanding diabetes and is associated with an increased morbidity and reduced quality of life in patients with diabetes. The present study evaluated the prevalence of CAN diagnosed by reduced heart rate variability (HRV) using a newly developed device in a large, unselected, hospital-based population of patients with diabetes. Methods: The study examined 323 patients consisting of 206 type 1 diabetes (T1DM) patients and 117 type 2 diabetes (T2DM) patients. The new handheld prototype Vagus™ was used to screen for CAN. Three different standardized cardiac reflex tests were performed to calculate HRV: 30:15 ratio, E:I ratio, and the Valsalva maneuver. An abnormal HRV in one test is indicative of early CAN, and if two or more tests show abnormal HRV, the diagnosis of CAN is established. Results: In total, 86% of examined patients completed all three tests. Each test was completed by more than 90% of the patients. The prevalence of established CAN was 23%, whereas 33% of the patients had early signs of CAN. The prevalence was higher in T2DM patients (27.8%) than in T1DM patients (20.6 %), p = . 02. Patients with CAN were older and had a longer duration of diabetes, higher systolic blood pressure, more nephropathy and retinopathy, and a higher vibration threshold. Conclusions: Cardiac autonomic neuropathy is frequent in both T2DM and T1DM patients, especially in those with other late diabetes complications. Screening for CAN with the new device is feasible.
Hardware acceleration of biomedical models with OpenCMISS and CellML

OpenCMISS is a mathematical modeling environment designed to solve field based equations and link subcellular and tissue-level biophysical processes to organ-level processes. It employs a general purpose parallel design, in particular distributed memory, for its computations. CellML is a mark up language based on XML that is designed to encode lumped parameter biophysically based systems of ordinary differential equations and nonlinear algebraic equations. OpenCMISS allows CellML models to be evaluated and integrated into models at various spatial and temporal scales. With good inherent parallelism, hardware acceleration based on FPGAs has a great potential to increase the computational performance and to reduce the energy consumption of computations with CellML models integrated in OpenCMISS. However, with several hundred CellML models, manual hardware implementation for each CellML model is complex and time consuming. The advantages of FPGA designs will only be realised if there is a general solution or a tool to automatically convert CellML models into hardware description languages such as VHDL. In this paper we describe the architecture for the FPGA hardware implementation of CellML models and evaluate the first results related to performance and resource usage based on a variety of criteria.
Concept-match medical data scrubbing. How pathology text can be used in research.

CONTEXT In the normal course of activity, pathologists create and archive immense data sets of scientifically valuable information. Researchers need pathology-based data sets, annotated with clinical information and linked to archived tissues, to discover and validate new diagnostic tests and therapies. Pathology records can be used for research purposes (without obtaining informed patient consent for each use of each record), provided the data are rendered harmless. Large data sets can be made harmless through 3 computational steps: (1) deidentification, the removal or modification of data fields that can be used to identify a patient (name, social security number, etc); (2) rendering the data ambiguous, ensuring that every data record in a public data set has a nonunique set of characterizing data; and (3) data scrubbing, the removal or transformation of words in free text that can be used to identify persons or that contain information that is incriminating or otherwise private. This article addresses the problem of data scrubbing. OBJECTIVE To design and implement a general algorithm that scrubs pathology free text, removing all identifying or private information. METHODS The Concept-Match algorithm steps through confidential text. When a medical term matching a standard nomenclature term is encountered, the term is replaced by a nomenclature code and a synonym for the original term. When a high-frequency "stop" word, such as a, an, the, or for, is encountered, it is left in place. When any other word is encountered, it is blocked and replaced by asterisks. This produces a scrubbed text. An open-source implementation of the algorithm is freely available. RESULTS The Concept-Match scrub method transformed pathology free text into scrubbed output that preserved the sense of the original sentences, while it blocked terms that did not match terms found in the Unified Medical Language System (UMLS). The scrubbed product is safe, in the restricted sense that the output retains only standard medical terms. The software implementation scrubbed more than half a million surgical pathology report phrases in less than an hour. CONCLUSIONS Computerized scrubbing can render the textual portion of a pathology report harmless for research purposes. Scrubbing and deidentification methods allow pathologists to create and use large pathology databases to conduct medical research.
3D ultrafast elastography imaging of the carotid artery using sparse arrays

Non-invasive Vascular Elastography (NIVE) using sparse arrays is a novel method for ultrafast elastography imaging of the carotid artery. Sparse array imaging retains the advantages of fully synthetic aperture imaging i.e. high lateral sensitivity, while overcoming its limitations of poor frame rate and high data volumes. In this study, we investigated the performance of a sparse array system comprising of only seven transmit elements in a dynamic motion regime. It was demonstrated, through simulation and experimental studies, that this technique can produce high quality axial and lateral displacement elastograms that can be used to compute accurate radial and circumferential strain elastograms. In this study, we compare the performance of elastograms obtained using a sparse array to those obtained with plane wave imaging. It was found that while plane wave imaging has a relatively higher frame rate and sonographic SNR, sparse array imaging provides better lateral displacement estimates resulting in superior strain elastograms.
Different Approaches of Spectral Subtraction Method for Speech Enhancement

: Enhancement of speech signal degraded by several types of noise is a topic of interest for last many years. The main aim of speech enhancement algorithm is to improve the quality and/or intelligibility of the noisy speech signals by using various techniques and algorithms. Among the all available methods, the spectral subtraction algorithm is the historically one of the first algorithm proposed for removing additive background noise. This paper presented the review of basic spectral subtraction algorithm, a short coming of basic spectral subtraction algorithm, different modified approaches of Spectral Subtraction Algorithms such as Spectral Subtraction with over subtraction factor, Non linear Spectral Subtraction, Multiband Spectral Subtraction, Minimum mean square Error Spectral Subtraction and Selective Spectral Subtraction that minimizes the shortcomings of the basic method, then performance evaluation of various modified spectral subtraction algorithms.
Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase 1 gene in nude mice

Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of matrix metalloproteinases (MMPs) that degrade extracellular matrix. We evaluated the metastatic ability of the highly metastatic human gastric cell line KKLS, and that of cells transfected with exogenous TIMP‐1 gene by the orthotopic transplantation model in nude mice.
Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia

Haploinsufficiency of 22q11 genes including catechol‐O‐methyltransferase (COMT) and proline dehydrogenase (PRODH) may result in structural and functional brain abnormalities and increased vulnerability to schizophrenia as observed in patients with microdeletions of 22q11. Thus, COMT and PRODH could be modifier genes for schizophrenia. We examined association of polymorphisms in COMT and PRODH with brain anatomy in young patients with schizophrenia and schizoaffective disorder. We acquired structural magnetic resonance imaging data from 51 male patients and genotyped two single nucleotide polymorphisms (SNPs) in the COMT gene and three in the PRODH gene. Statistical Parametric Mapping software and optimized voxel‐based morphometry were used to determine regional gray matter (GM) and white matter (WM) density differences, and total GM and WM volume differences between genotype groups. Two nonsynonymous SNPs in the PRODH gene were associated with bilateral frontal WM density reductions and an SNP in the P2 promoter region of COMT (rs2097603) was associated with GM increase in the right superior temporal gyrus. Furthermore, we found evidence for COMT and PRODH epistasis: in patients with a COMT Val allele (rs4680) and with one or two mutated PRODH alleles, we observed increased WM density in the left inferior frontal lobe. Our results suggest that genetic variation in COMT and PRODH has significant effects on brain regions known to be affected in schizophrenia. Further research is needed to investigate the role of 22q11 genes on brain structure and function and their role in vulnerability for schizophrenia.
Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells.

The diterpene, forskolin [half-maximal effective concentration (EC50), 5-10 microM] activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6. 1.1] in rat cerebral cortical membranes in a rapid and reversible manner. Activation is not dependent on exogenous guanyl nucleotides and is not inhibited by guanosine 5'-O-(2-thiodiphosphate) when assayed with adenosine 5'-[beta, gamma-imido]triphosphate as substrate. GTP and GDP potentiate responses to forskolin. The activations of adenylate cyclase by forskolin and guanosine 5'-[beta, gamma-imido]triphosphate p[NH]ppG are not additive, whereas activations by forskolin and fluoride are additive or partially additive. The responses of adenylate cyclase to forskolin or fluoride are not inhibited by manganese ions, whereas the response to p[NH]ppG is completely blocked. Activation of adenylate cyclase by forskolin is considerably greater than the activation by fluoride in membranes from rat cerebellum, striatum, heart, and liver, while being about equal or less than the activation by fluoride in other tissues. Forskolin (EC50, 25 microM) causes a rapid and readily reversible 35-fold elevation of cyclic AMP in rat cerebral cortical slices that is not blocked by a variety of neurotransmitter antagonists. Low concentrations of forskolin (1 microM) augment the response of cyclic AMP-generating systems in brain slices to norepinephrine, isoproterenol, histamine, adenosine, prostaglandin E2, and vasoactive intestinal peptide. Forskolin would appear to activate adenylate cyclase through a unique mechanism involving both direct activation of the enzyme and facilitation or potentiation of the modulation of enzyme activity by receptors or the guanyl nucleotide-binding subunit, or both.
Effect of electrical stimulation on chronic leg ulcer size and appearance.

BACKGROUND AND PURPOSE Electrical current has been recommended for use on chronic pressure ulcers; however, the ability of this modality to improve healing of other types of chronic ulcers is less well established. The purpose of this study was to examine the effect of high-voltage pulsed current (HVPC) on healing of chronic leg ulcers. SUBJECTS Twenty-seven people with 42 chronic leg ulcers participated in the study. METHODS The subjects were separated into subgroups according to primary etiology of the wound (diabetes, arterial insufficiency, venous insufficiency) and then randomly assigned to receive either HVPC (100 microseconds, 150 V, 100 Hz) or a sham treatment for 45 minutes, 3 times weekly, for 4 weeks. Wound surface area and wound appearance were assessed during an initial examination, following a 1- to 2-week period during which subjects received only conventional wound therapy, after 4 weeks of sham or HVPC treatment, and at 1 month following treatments. RESULTS The results indicated that HVPC applied to chronic leg ulcers reduced the wound surface area over the 4-week treatment period to approximately one half the initial wound size (mean decrease=44.3%, SD=8.8%, range=2.8%-100%), which was over 2 times greater than that observed in wounds treated with sham units (mean decrease=16.0%, SD=8.9%, range=-30.3%-83.7%). DISCUSSION AND CONCLUSION The results of the study indicate that HVPC administered 3 times a week should be considered to accelerate wound closure of chronic leg ulcers.
Adult adoptees and considerations of parenthood : an exploratory study examining adoption experiences and effects

This exploratory, qualitative study sought to investigate how the experience of adoption affects an adoptee’s decision to start a family (or not). One reason to conduct this study was to isolate a particular developmental stage – entering parenthood – to observe deliberations related to the experience of being adopted. This study adds to the limited but growing body of research dedicated to adult adoptees with the aim of assisting clinicians in the field of social work to enhance their knowledge about the experiences of adopted people, especially those who are considering starting a family. The study was conducted by interviewing seventeen adult adoptees who were: adopted as an infant, either domestically or internationally; were at least eighteen; and were contemplating starting a family or were parents already. The study was designed to elicit information about the participants’ adoption narratives in order to observe if connections exist between their adoption experiences and considerations of starting a family. The major finding of this project is that, though the participants agreed their family planning decisions were affected by their adoptive experience, they were not ultimately hindered in their parenting choices by any lasting effects of adoption. Participants often recounted how either their idyllic childhoods provided inspiration for becoming a parent or their experiences as adoptees promoted a desire to address adoption-related emotional injuries.