Miracle-dz/UniFAR-FTUs huggingface dataset:
Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors

Romidepsin is a histone deacetylase inhibitor (HDI), approved by the US FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Although various mechanisms have been proposed for the activity of HDIs, including induction of genes controlling cell cycle, acetylation of cytoplasmic proteins and direct induction of apoptosis, the mechanism underlying activity of romidepsin and other HDIs in CTCL is not known. Romidepsin induces long-lasting responses. The side-effect profile is similar to that of other HDIs, causing fatigue, nausea and thrombocytopenia. Management of the CTCL population requires vigilence to prevent infection with skin contaminants, and monitoring of potassium and magnesium, electrolytes found to be low in a large proportion of patients. Electrocardiographic (ECG) changes are common but are not associated with myocardial damage. When molecular end points were evaluated in 61 patients enrolled on a Phase II trial with romidepsin, response was associated with persistence of acetylated histone H3, suggesting that drug exposure is important in effective therapy with romidepsin. Future studies will endeavor to identify combination strategies to increase the efficacy both in resistant CTCL and in solid tumors and to identify biomarkers of response that will allow selection of patients most likely to benefit from the therapy.
Outage Analysis of NOMA-HCN Using Repulsive Point Process

The current literature characterizes the performance gain achieved by non-orthogonal multiple access (NOMA) using stochastic geometry based on the assumption of Poisson Point Processes (PPP) to model the spatial distribution of base stations. This paper develops an analytical framework to analyze the gain achieved by NOMA in a heterogeneous cellular network (HCN) consisting of a macro base station (MBS) tier and a femto base station (FBS) tier modeled using repulsive point process namely modified hard core point process (MoHCPP). It is observed that modeling NOMA network using MoHCPP approach decreases the outage probability by $ 74.04 \% $ for a cell center user (CCU) and by $48.65 \%$ for a cell edge user (CEU) as compared to NOMA using PPP. This improvement is attributed to decrease in dominant interferers due to thinning process of MoHCPP. It is also observed that with the increase in FBS density the advantage of NOMA with MoHCPP modeling is more for CEU as compared CCU due to additional benefit of dense FBSs for CEU. Hence, it is inferred that high density FBS network with NOMA modeled using MoHCPP proves to be better suited for CEU as compared to PPP modeling. The results for the proposed NOMA with MoHCPP model are also verified using simulations.
Pharmacist's role in a Parkinson's disease and movement disorders clinic.

PURPOSE The expanding role of a clinical pharmacist at a Veterans Affairs (VA) out-patient clinic for patients with Parkinson's disease (PD) and movement disorders is described. SUMMARY San Francisco VA Medical Center added a clinical pharmacist to the multi-disciplinary team serving patients at an outpatient clinic operated by its Parkinson's Disease Research, Education and Clinical Center (PADRECC). During the first six months after joining the clinic team, the pharmacist met with 131 patients and made a total of 69 drug therapy recommendations that were implemented by neurologists, clinical nurse specialists, and other PADRECC providers. The results of a retrospective chart review suggested that in about 21% of the cases evaluated, the pharmacist's recommendations contributed to an improved medical outcome or the resolution of a medical problem. Anonymous surveys indicated that clinic providers (n = 33) and patients (n = 20) were satisfied with the pharmacist's services. Using a five-point Likert scale (scores ranged from 1 for "strongly disagree" to 5 for "strongly agree") that they had more time to devote to other clinic responsibilities with the pharmacist present in the clinic (mean score, 4.79); patients indicated that they had an improved understanding of their medications after speaking with the pharmacist (mean score, 4.88). CONCLUSION A clinical pharmacist's regular involvement in an outpatient PD and movement disorders clinic has been well received by patients and clinic providers. The study results suggest that the pharmacist has made important contributions in areas such as therapeutic problem solving and medication education while freeing up providers for other responsibilities.
Analysis of the Repressor Element‐1 Silencing Transcription Factor/Neuron‐Restrictive Silencer Factor Occupancy of Non‐Neuronal Genes in Peripheral Lymphocytes from Patients with Huntington's Disease

We have previously demonstrated that the transcription of neuronal repressor element‐1/neuron‐restrictive silencer element (RE1/NRSE)‐regulated genes is reduced in the brain of subjects with Huntington's disease (HD) as a result of increased binding of the repressor element‐1 silencing transcription factor/neuron‐restrictive silencer factor (REST/NRSF) to its RE1/NRSE targets. As specific non‐neuronal REST/NRSF‐regulated genes have been identified in the human genome, we exploited the possibility that the binding of REST/NRSF to its target RE1/NRSE sites may also be altered in the peripheral tissues of HD patients.
Yeast pip3/mec3 mutants fail to delay entry into S phase and to slow DNA replication in response to DNA damage, and they define a functional link between Mec3 and DNA primase

The catalytic DNA primase subunit of the DNA polymerase alpha-primase complex is encoded by the essential PRI1 gene in Saccharomyces cerevisiae. To identify factors that functionally interact with yeast DNA primase in living cells, we developed a genetic screen for mutants that are lethal at the permissive temperature in a cold-sensitive pril-2 genetic background. Twenty-four recessive mutations belonging to seven complementation groups were identified. Some mutants showed additional phenotypes, such as increased sensitivity to UV irradiation, methyl methanesulfonate, and hydroxyurea, that were suggestive of defects in DNA repair and/or checkpoint mechanisms. We have cloned and characterized the gene of one complementation group, PIP3, whose product is necessary both for delaying entry into S phase or mitosis when cells are UV irradiated in G1 or G2 phase and for lowering the rate of ongoing DNA synthesis in the presence of methyl methanesulfonate. PIP3 turned out to be the MEC3 gene, previously identified as a component of the G2 DNA damage checkpoint. The finding that Mec3 is also required for the G1- and S-phase DNA damage checkpoints, together with the analysis of genetic interactions between a mec3 null allele and several conditional DNA replication mutations at the permissive temperature, suggests that Mec3 could be part of a mechanism coupling DNA replication with repair of DNA damage, and DNA primase might be involved in this process.
Loss of downregulated in adenoma (DRA) impairs mucosal HCO3− secretion in murine ileocolonic inflammation

Background: Ileocolonic luminal pH has been reported to be abnormally low in inflammatory bowel disease (IBD) patients, and one of the causative factors may be reduced epithelial HCOSymbol secretory rate (JSymbol). Disturbances in JSymbol may occur due to inflammation‐induced changes in the crypt and villous architecture, or due to the effect of proinflammatory cytokines on epithelial ion transporters. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Methods: To discriminate between these possibilities, the tumor necrosis factor alpha (TNF‐&agr;) overexpressing (TNF+/&Dgr;ARE) mouse model was chosen, which displays high proinflammatory cytokine levels in both ileum and colon, but develops only mild colonic histopathology and diarrhea. HCOSymbol secretion, mRNA expression, immunohistochemistry, and fluid absorptive capacity were measured in ileal and mid‐colonic mucosa of TNF+/&Dgr;ARE and wildtype (WT) (TNF+/+) mice in Ussing chambers, and in anesthetized mice in vivo. Symbol. No caption available. Results: The high basal JSymbol observed in WT ileal and mid‐colonic mucosa were luminal Cl−‐dependent and strongly decreased in TNF+/&Dgr;ARE mice. Downregulated in adenoma (DRA) mRNA and protein expression was strongly decreased in TNF+/&Dgr;ARE ileocolon, whereas cystic fibrosis transmembrane conductance regulator (CFTR), Na+/H+ exchanger 3 (NHE3), Na+/HCOSymbol cotransporter (NBC), and epithelial sodium channel (ENaC) expression was not significantly altered. This indicates that the severe defect in ileocolonic JSymbol was due to DRA downregulation. Fluid absorption was severely depressed in the ileum but only mildly affected in the mid‐distal colon, preventing the development of overt diarrhea. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Conclusions: Even mild ileocolonic inflammation may result in a decrease of epithelial HCOSymbol secretion, which may contribute to alterations in surface pH, intestinal flora, and mucus barrier properties. (Inflamm Bowel Dis 2011;) Symbol. No caption available.
The Effect of Injury on Rotational Coupling at the Lumbosacral Joint: A Biomechanical Investigation

The lumbosacral joint is frequently indicated as a source of low-back pain, a cause of which may be abnormal patterns of vertebral motions. The goal of this study was to describe the influence of injury on the coupled motions of the L5-S1 joint in a human cadaveric model. Nine whole lumbosacral spine specimens were studied under the application of flexion, extension, left/right axial torque and right/left lateral bending pure moments. Injuries to the posterior ligaments, intervertebral disc, and articular facets at L5-S1 were produced, and the motion at L5-S1 was determined after each sequential injury. No significant coupled rotations were observed under flexion or extension moments. Under axial torque, lateral rotation at L5-S1 occurred to the same side as the applied torque and increased significantly only after injury to the intervertebral disc. Also coupled to axial torque was flexion rotation in the intact specimen, which became extension rotation after facetectomy. Under lateral bending moments, coupled axial rotation was to the opposite side of the applied moment and increased significantly only after removal of the facets of L5. Based on these results, it was concluded that intervertebral disc most resisted the coupled motion of lateral rotation under the application of axial torque, whereas the articular facets most resisted the coupled axial rotation under the application of lateral bending at the lumbosacral joint. Also, the facets were the structures that produced the flexion rotation of L5 on S1 under axial torque loading.
An innovative approach for monitoring elderly behavior by detecting home appliance's usage

Detecting how elderly people interact with their surrounding environment, especially with domestic electrical appliances, is an important parameter to assess Mild Cognitive Impairments and frailty issues. This paper proposes an innovative approach for monitoring elderly behavior by detecting home appliance's usage. It is based on an unobtrusive smart meter that periodically measures the global power consumption in the house, associated with some smart plugs for punctually monitoring specific electrical devices. This infrastructure has been implemented and validated within the Personal Data Capturing System of the City4Age Platform, where, joined with other provided monitoring systems, can feed risk detection algorithms with more accurate data. Summarizing, implemented system, although simple and at low cost, is able to combine data provided by designed power meter with those of smart meter plugs and, by means of implemented algorithms, to detect unusual elder behavior, moreover resulting reliable and accurate.
Strong population structure in the marine sponge Crambe crambe (Poecilosclerida) as revealed by microsatellite markers

Different categories of molecular markers have been used so far to study the population structure of sponges. However, these markers often did not have the resolution power to address precisely questions on structuring processes, especially at the intrapopulational level. In this study we show that microsatellites fulfil these expectations, allowing a fine description of population structure at different geographical scales in the marine sponge Crambe crambe. Specimens were collected in 11 locations, representing most of the Atlanto‐Mediterranean range of the species, and were analysed at six loci. As expected for a sessile invertebrate with lecitotrophic larvae, high levels of between‐population structure were found (FST = 0.18) and a significant isolation‐by‐distance pattern was observed. A strong genetic structure was also found within sampled sites (FIS = 0.21) that may be explained by several factors including inbreeding, selfing and the Wahlund effect. In spite of a sampling design planned to avoid the sampling of clones, genotypically identical individuals for the six loci were found in some locations. The significance of these potential clones is discussed and their effect on the observed pattern of population structure assessed. Patterns of allelic distribution within populations suggest the possibility of a recent colonization of the Atlantic range from the Mediterranean Sea.
Recombinational construction in Escherichia coli of infectious adenoviral genomes.

A two-step gene replacement procedure was developed that generates infectious adenoviral genomes through homologous recombination in Escherichia coli. As a prerequisite, a human adenovirus serotype 5 (Ad5)-derived genome was first introduced as a PacI restriction fragment into an incP-derived replicon which, in contrast to ColE1-derivatives (e.g., pBR322 or pUC plasmids), is functional in a polA mutant of E. coli. Any modification can be introduced at will following two consecutive homologous recombinations between the incP/Ad5 replicon and the ColE1 plasmid. The overall procedure requires only the in vitro engineering of the ColE1-derivative by flanking the desired modification with small stretches of identical sequences. In the first step, a cointegrate between the tetracycline-resistant incP/Ad5 replicon and the kanamycin-resistant ColE1-derivative is selected by growing the polA host in the presence of both antibiotics. Resolution of this cointegrate is further selected in sucrose growth conditions due to the loss of a conditional suicide marker (the sacB gene of Bacillus subtilis) present in the ColE1 plasmid, leading to unmodified and modified incP/Ad5 replicons that can be differentiated upon restriction analysis. Consecutive rounds of this two-step cloning procedure allowed the introduction of multiple independent modifications within the virus genome, with no requirement for an intermediate virus. The potential of this procedure is demonstrated by the recovery of several E1E3E4-deleted adenoviruses following transfection of the corresponding E. coli-derived genomes in IGRP2 cells.
A General Auxiliary Controller for Multi-agent Flocking

We aim to improve the performance of multi-agent flocking behavior by quantifying the structural significance of each agent. We designed a confidence score(ConfScore) to measure the spatial significance of each agent. The score will be used by an auxiliary controller to refine the velocity of agents. The agents will be enforced to follow the motion of the leader agents whose ConfScores are high. We demonstrate the efficacy of the auxiliary controller by applying it to several existing algorithms including learning-based and non-learning-based methods. Furthermore, we examined how the auxiliary controller can help improve the performance under different settings of communication radius, number of agents and maximum initial velocity.
Abnormal human activity recognition system based on R-transform and kernel discriminant technique for elderly home care

Video sensor based human activity recognition systems have potential applications in life care and health care areas. The paper presents a system for elderly care by recognizing six abnormal activities; forward fall, backward fall, chest pain, faint, vomit, and headache, selected from the daily life activities of elderly people. Privacy of elderly people is ensured by automatically extracting the binary silhouettes from video activities. Two problems are addressed in this research, which decrease recognition accuracy during the process of abnormal human activity recognition (HAR) system development. First, the problem of continuous changing distance of a moving person from two viewpoints is resolved by using the R-transform. R-transform extracts periodic, scale and translation invariant features from the sequences of activities. Second, the high similarities in postures of different activities is significantly improved by using the kernel discriminant analysis (KDA). KDA increases discrimination between different classes of activities by using non-linear technique. Hidden markov model (HMM) is used for training and recognition of activities. The system is evaluated against linear discriminant analysis (LDA) on the original silhouette features and LDA on the R-transform features. Average recognition rate of 95.8% proves the feasibility of the system for elderly care at home.
Molecular exploration of hidden diversity in the Indo-West Pacific sciaenid clade

The family Sciaenidae, known as croakers or drums, is one of the largest perciform fish families. A recent multi-gene based study investigating the phylogeny and biogeography of global sciaenids revealed that the origin and early diversification of this family occurred in tropical America during the Late Oligocene—Early Miocene before undergoing range expansions to other seas including the Indo-West Pacific, where high species richness is observed. Despite this clarification of the overall evolutionary history of the family, knowledge of the taxonomy and phylogeny of sciaenid genera endemic to the Indo-West Pacific is still limited due to lack of a thorough survey of all taxa. In this study, we used DNA-based approaches to investigate the evolutionary relationships, to explore the species diversity, and to elucidate the taxonomic status of sciaenid species/genera within the Indo-West Pacific clade. Three datasets were herein built for the above objectives: the combined dataset (248 samples from 45 currently recognized species) from one nuclear gene (RAG1) and one mitochondrial gene (COI); the dataset with only RAG1 gene sequences (245 samples from 44 currently recognized species); and the dataset with only COI gene sequences (308 samples from 51 currently recognized species). The latter was primarily used for our biodiversity exploration with two different species delimitation methods (Automatic Barcode Gap Discovery, ABGD and Generalized Mixed Yule Coalescent, GMYC). The results were further evaluated with help of four supplementary criteria for species delimitation (genetic similarity, monophyly inferred from individual gene and combined data trees, geographic distribution, and morphology). Our final results confirmed the validity of 32 currently recognized species and identified several potential new species waiting for formal descriptions. We also reexamined the taxonomic status of the genera, Larimichthys, Nibea, Protonibea and Megalonibea, and suggested a revision of Nibea and proposed a new genus Pseudolarimichthys.
In vitro activity of AT-4140 against clinical bacterial isolates

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.
Recent advances in the development of a chemically synthesised anti-malarial vaccine

Introduction: Obtaining an effective antimalarial vaccine has represented one of the biggest public health challenges over the last 50 years. Despite efforts by many laboratories around the world using whole-organism, recombinant proteins and genome-based approaches, the results have been disappointing. One of the main problems when designing an antimalarial vaccine is the poor immunogenicity induced by the functionally relevant and conserved protein regions of the parasite. Areas covered: This review focuses on the logical and rational methodology followed to identify Plasmodium falciparum conserved functional regions with the ability to bind to target cells conserved high activity binding peptides (cHABPs) and the physicochemical and immunological characteristics that should be taken into account for modifying them into highly immunogenic and protection-inducing peptides (mHABPs) into highly immunogenic and protection-inducing in Aotus monkeys. Expert opinion: The functional approach taken to develop a fully protective, minimal subunit-based, multiantigenic, multistage and synthetic peptide-based antimalarial vaccine has shown promising results. The clear relationship observed between mHABPs structure and their immunological properties highlights the challenges and opportunities arising from this methodology, as well as the universal principles and rules derived therefrom.
Patients' perceptions of need for primary health care services: useful for priority setting?

Abstract Objectives: To assess the feasibility of using patients' perceptions of need for primary health care services to develop priorities. Design: A postal survey of a random sample of 3478 patients registered with five general practices. Setting: Lothian, Scotland. Main outcome measures: Comparison of rankings of 36 different kinds of help or advice according to (a) popularity in the sample size as a whole and in healthy and unhealthy subgroups and (b) health status (severity of need) of potential service users. Results: Popularity rankings differed between the healthy and unhealthy subgroups and the whole sample. Popularity rankings were almost the inverse of rankings based on health status. The analysis identified two areas of substantial need both in terms of popularity and severity: pain management and advice about welfare benefits. Conclusions: Methodological efforts to ensure equal participation in the processes of assessing health needs and of priority setting do not in themselves promote equity. To promote equity some opinions may need to be given greater weight. Key messages Key messages The ranked popularity of services was different for a group of healthy people than for a group of unhealthy people Priorities for services based on popularity were different from those based on severity of need A great danger exists that the needs of minority groups are neglected if too much emphasis is placed on giving everyone an equal say All methods of assessment of health needs and priority setting should be explicit about principles of equity