Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk Assessment and Prevention of Pressure Ulcers

TO THE EDITOR: Qaseem and colleagues (1) effectively summarize the strength of evidence supporting pressure ulcer prevention, which is only weak to moderate in most cases. We agree with their recommendation that clinicians should assess all hospitalized patients to identify those at risk for pressure ulcers. How this first step is implemented is important in order to initiate other components of evidence-based practices as indicated by the Wound, Ostomy and Continence Nurses Society, as well as the National Pressure Ulcer Advisory Panel (NPUAP), European Pressure Ulcer Advisory Panel, and Pan Pacific Pressure Injury Alliance in the 2014 international guidelines for pressure ulcer prevention (2, 3). Qaseem and colleagues reviewed several risk assessment instruments, including the Braden, Cubbin and Jackson, Norton, Ramstadius, and Waterlow scales, and found that the Braden and Norton scales possessed good-quality evidence for prognosis of risk (1). However, these instruments lacked subscales that would differentiate patient risk on the basis of sociodemographic characteristics or clinical setting. In addition, a recent meta-analysis by Garca-Fernndez and associates found that the Braden scale has the most validation studies and shows a capacity to predict pressure ulcers (4). Good predictive capacity was found for the Norton scale, as well. In fact, Garca-Fernndez and associates' meta-analysis of 4 studies with a pooled sample of 1500 patients determined that clinical judgment alone inadequately assessed risk for pressure ulcers. Although current evidence is inconclusive about the direct association between risk assessment and a decrease in pressure ulcer, the evidence does support the use of validated pressure ulcer risk assessment tools, such as the Braden or Norton scales, in conjunction with clinical judgment (24). Qaseem and colleagues' guideline should not deter any providers from using these instruments, even those with expert gestalt. Staff nurses, for example, should become comfortable using the best available structured instruments to carry out risk assessment. Likewise, those with clinical expertise who are revered by others with less experience should strive to establish a benchmark for best practices in quality improvement by synergizing their judgment with the strengths of risk assessment instruments (5). Clinical practice guidelines, such as these preventive recommendations from the American College of Physicians, need to align providers with national best practices and the use of structured instruments even when the science to support their use is continuing to grow and strengthen. As the field of nursing continues to investigate improved population-based risk assessment instruments as part of evidence-based practices, training providers to use structured instruments as opposed to clinical judgment will make a transition to modern instruments more seamless.
The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation*

DNA methylation plays an important role in mammalian development and correlates with chromatin-associated gene silencing. The recruitment of MeCP2 to methylated CpG dinucleotides represents a major mechanism by which DNA methylation can repress transcription. MeCP2 silences gene expression partly by recruiting histone deacetylase (HDAC) activity, resulting in chromatin remodeling. Here, we show that MeCP2 associates with histone methyltransferase activity in vivo and that this activity is directed against Lys9 of histone H3. Two characterized repression domains of MeCP2 are involved in tethering the histone methyltransferase to MeCP2. We asked if MeCP2 can deliver Lys9 H3 methylation to the H19 gene, whose activity it represses. We show that the presence of MeCP2 on nucleosomes within the repressor region of the H19 gene (the differentially methylated domain) coincides with an increase in H3 Lys9methylation. Our data provide evidence that MeCP2 reinforces a repressive chromatin state by acting as a bridge between two global epigenetic modifications, DNA methylation and histone methylation.
A 0.45-V Low-Power OOK/FSK RF Receiver in 0.18  $\mu\text{m}$ CMOS Technology for Implantable Medical Applications

A 0.45-V low-power 0.18 μm CMOS OOK/FSK RF receiver for implantable medical applications is proposed. The receiver utilizes a wake-up mechanism to adjust its power consumption automatically by reading the amplitude of the input wireless OOK/FSK modulated RF signal directly. No additional wireless wake-up commands are required. Such a normally-off and instanton scheme reduces the power consumption of this receiver significantly. The power consumption is 129 μW in sleep mode and 352 μW in wake-up mode. Other techniques, such as third-orderharmonic cancellation, subharmonic mixing, and forward body biasing are also adopted for better linearity, higher LO-to-RF isolation, and lower VDD, respectively. The measurement results show that the proposed receiver consumes only 2.6 nJ/bit (OOK) and 1 nJ/bit (FSK) to achieve the sensitivities of -55 dBm (OOK) and -53.5 dBm (FSK) in BER <; 10-3 constraint. The proposed receiver is designed for low-power and short-distance MICS band applications.
Differential Modulation of Reinforcement Learning by D2 Dopamine and NMDA Glutamate Receptor Antagonism

The firing pattern of midbrain dopamine (DA) neurons is well known to reflect reward prediction errors (PEs), the difference between obtained and expected rewards. The PE is thought to be a crucial signal for instrumental learning, and interference with DA transmission impairs learning. Phasic increases of DA neuron firing during positive PEs are driven by activation of NMDA receptors, whereas phasic suppression of firing during negative PEs is likely mediated by inputs from the lateral habenula. We aimed to determine the contribution of DA D2-class and NMDA receptors to appetitively and aversively motivated reinforcement learning. Healthy human volunteers were scanned with functional magnetic resonance imaging while they performed an instrumental learning task under the influence of either the DA D2 receptor antagonist amisulpride (400 mg), the NMDA receptor antagonist memantine (20 mg), or placebo. Participants quickly learned to select (“approach”) rewarding and to reject (“avoid”) punishing options. Amisulpride impaired both approach and avoidance learning, while memantine mildly attenuated approach learning but had no effect on avoidance learning. These behavioral effects of the antagonists were paralleled by their modulation of striatal PEs. Amisulpride reduced both appetitive and aversive PEs, while memantine diminished appetitive, but not aversive PEs. These data suggest that striatal D2-class receptors contribute to both approach and avoidance learning by detecting both the phasic DA increases and decreases during appetitive and aversive PEs. NMDA receptors on the contrary appear to be required only for approach learning because phasic DA increases during positive PEs are NMDA dependent, whereas phasic decreases during negative PEs are not.
Pharmacokinetics and Safety of AMD-3100, a Novel Antagonist of the CXCR-4 Chemokine Receptor, in Human Volunteers

ABSTRACT AMD-3100, a bicyclam, is a novel agent that uniquely inhibits the entry of human immunodeficiency virus type 1 (HIV-1) into CD4+ T cells via selective blockade of the chemokine CXCR-4 receptor. Twelve healthy volunteers were given AMD-3100 as a single 15-min intravenous infusion at 10, 20, 40, or 80 μg/kg. Five subjects also received a single subcutaneous injection of AMD-3100 (40 or 80 μg/kg). Three subjects received two escalating oral doses each (80 and 160 μg/kg). All subjects tolerated their dose(s) well without any grade 2 toxicity or dose adjustment. Six subjects experienced mild, transient symptoms, primarily gastrointestinal in nature and not dose related. All subjects experienced a dose-related elevation of the white blood cell count, from 1.5 to 3.1 times the baseline, which returned to the baseline 24 h after dosing. AMD-3100 demonstrated dose proportionality for the maximum drug concentration in serum (Cmax) and the area under the concentration-time curve from 0 h to ∞ (AUC0–∞) over the entire dose range. At the highest intravenous dose (80 μg/kg), the medianCmax was 515 (range, 470 to 521) ng/ml and the AUC0–∞ was 1,044 (range, 980 to 1,403) ng-h/ml. The median systemic absorption after subcutaneous dosing was 87% (range, 67 to 106%). No drug was detectable in the blood following oral dosing. Using a two-compartment model, the median pharmacokinetic parameter estimates (ranges) were as follows: volume of distribution, 0.34 (0.27 to 0.36) liter/kg; clearance, 1.30 (0.97 to 1.34) liters/h; elimination half-life, 3.6 (3.5 to 4.9) h. After a single, well-tolerated intravenous dose of AMD-3100, concentrations were sustained for 12 h above the in vitro antiretroviral 90% inhibitory concentrations and for 8 h above antiviral concentrations identified in the SCID-hu Thy/Liv mouse model of HIV infection.
Bearings-Only Localization with NLOS Reflected AoAs

Sensor networks enable the localization of a target (or source) of interest with spatially complementary observations. Current available physical measurements include received signal strength [1], time of arrival [11], angle of arrival (AoA) [6, 7, 10, 13, 19], and so forth. They can be individually or cooperatively utilized in target information extraction. In this paper, we concentrate on localizing a single target with distributed AoAs, specifically bearings-only localization. Bearings-only localization infers the position of a target with multiple AoA lines, which share a unique intersection–the target location–in the absence of noise. If observation uncertainty is included, a global intersection may not exist and advanced estimators are required. Least squares (LS) is a straightforward choice if the noise distribution is unknown [6]. If noise statistics are known, maximum likelihood (ML) is an option and is popular [10, 13]. Its good performance is guaranteed at the cost of computational load. The Stansfield estimator is a kind of weighted LS for independent Gaussian noise [19]; it is a compromise between estimation performance and computation. Reference [10] shows that the root mean square errors (RMSEs) of a Stansfield estimator are not necessarily larger than those of ML in bearings-only localization. Other approaches include total least squares [7], and so forth. The aforementioned works focus on line-of-sight (LOS) propagation, where a direct path exists between the target and sensors; nevertheless, practical problems may not necessarily have a LOS. When the wavefront (acoustic, light, or electromagnetic) of target radiation meets an interface between two media, reflection will happen [14]. The reflection is helpful for the extraction of target information in some circumstances, especially where LOS propagation is unavailable. An interesting application is over-the-horizon radar (OTHR) [9, 17] (see Fig. 1). If multiple geometrically complementary radar sensors are available, a fusion center can infer the position of the target with proper data association.1 Instead of LOS AoAs, this paper studies the localization with non-line-of-sight (NLOS) reflection measurements, where the radiation from a target reaches a sensor after a single specular reflection.
Genotoxicity of engineered nanomaterials: A critical review

In view of the fast-growing industrial applications of engineered nanomaterials (ENMs), the evaluation of their genotoxic potential and of their mode of action is a necessity to conduct adequate hazard/risk assessment and to produce safer and sustainable ENMs. This review aims at: (i) Providing an evaluation of in vitro and in vivo genotoxicity data available for ENM, and (ii) proposing minimal criteria for conducting nano-genotoxicity assays. The possible modes of action of ENM (i.e., generation of reactive oxygen species (ROS) and mechanical interference with cellular components) and the potential cellular targets are discussed. The available studies are evaluated on the basis of specific quality criteria after categorisation according to ENMs type/size investigated. No definitive conclusion can be drawn concerning the genotoxic activity of ENMs, essentially because of the limited number of data, incomplete physico-chemical characterization of ENMs examined and shortcomings in experimental approaches. This evaluation revealed gaps to be considered in future studies (e.g., one-sided approach focusing mainly on ROS as mode of action) and the need to develop adequate positive controls for genotoxicity assays when conducted with nanomaterials.
A Probabilistic Modeling Approach for Uncovering Neural Population Rotational Dynamics

An important task in computational neuroscience is to understand neural representations of population codes, using either Bayesian approach or dynamical systems approach. We provide a probabilistic interpretation of the jPCA algorithm, recently proposed by Churchland et al. [1] for revealing the rotational patterns and dynamics in neuronal population activity. Using the jPCA technique, the authors showed that neural firing rates during reaching tasks (a non-rhythmic activity) exhibit a quasi-periodic pattern. Here we show that the original jPCA algorithm can be formulated as a linear algebra problem, and therefore be solved using the well-known technique of polar decomposition. Moreover, we show that the technique can be cast into a probabilistic framework which allows for application of Bayesian methods for model identification and parameter fitting. Moreover, missing data also can be handled within this framework using an expectation-maximization approach. Our approach provides an alternative yet more robust approach for dimensionality reduction and visualization in analyzing noisy neural population codes.
Automatic Generation of Visual Programming Environments

We have developed the visual language compiler-compiler (VLCC) system to automatically generate visual programming environments. VLCC is a grammar based system that can support implementation of any visual language by assisting the language designer in defining the language's graphical objects, syntax, and semantics. The final result of the generation process includes an integrated environment with a visual editor and a compiler for the defined visual language. In VLCC, graphical tools define visual languages to create both graphical objects and composition rules. Visual editors enable language designers to directly and visually manipulate the syntax of these languages. To capture the widest range of visual languages, the VLCC system can be configured for a specific language class. Different language classes can be characterized depending on their graphical objects' structure and on the way they can be composed. Also, box and arrow diagrams are defined for primitive objects with attaching points and for composition rules to join boxes and arrows at those attaching points. After choosing the visual language type to create, the designer can concentrate on language definition details. VLCC uses the positional grammar model as its underlying grammar formalism. >
Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β

Background There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression. Methodology/Principal Findings Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1β is associated with a selective reduction in Mitofusin 2 (Mfn2) expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1β increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1β-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1β increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor α (ERRα). Conclusions/Significance Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1β in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.
Bacterial vaginosis Transmission, role in genital tract infection and pregnancy outcome: an enigma

Whether bacterial vaginosis (BV) is acquired from an endogenous or an exogenous source is subject to controversy. Despite findings of an association between sexual behaviour and BV, some data indicate that BV is not a sexually transmitted infection in the traditional sense, while other data indicate that BV is an exogenous infection. A third aspect of BV is its tendency to go unnoticed by affected women. All of this will have a strong impact on how physicians view the risks of asymptomatic BV. This review focuses on whether or not BV should be regarded as a sexually transmitted infection (STI), its role in postoperative infections and pelvic inflammatory disease (PID), and on whether or not treatment of BV during pregnancy to reduce preterm delivery should be recommended. The reviewed studies do not lend unequivocal support to an endogenous or exogenous transmission of the bacteria present in BV. For women undergoing gynaecological surgery such as therapeutic abortion, the relative risk of postoperative infection is clearly elevated (approx. 2.3–2.8). A weaker association exists between BV and pelvic inflammatory disease. Data on treatment of BV as a way of reducing preterm delivery are inconclusive and do not support recommendations for general treatment of BV during pregnancy. The discrepant associations between BV and preterm birth found in recent studies may be explained by variations in immunological response to BV. Genetic polymorphism in the cytokine response – both regarding the TNF alleles and in interleukin production – could make women more or less susceptible to BV, causing different risks of preterm birth. Thus, studies on the vaginal inflammatory response to microbial colonization should be given priority.
Analysis of RTM Extended Images for VTI Media

ABSTRACTExtended images obtained from reverse time migration (RTM) contain information about the accuracy of the velocity field and subsurface illumination at different incidence angles. Here, we evaluate the influence of errors in the anisotropy parameters on the shape of the residual moveout (RMO) in P-wave RTM extended images for VTI (transversely isotropic with a vertical symmetry axis) media. Using the actual spatial distribution of the zero-dip NMO velocity (Vnmo), which could be approximately estimated by conventional techniques, we analyze the extended images obtained with distorted fields of the parameters η and δ. Differential semblance optimization (DSO) and stack-power estimates are employed to study the sensitivity of focusing to the anisotropy parameters. We also build angle gathers to facilitate interpretation of the shape of RMO in the extended images. The results show that the signature of η is dip-dependent, whereas errors in δ cause defocusing only if that parameter is laterally varying.
The syntactical image of the city:a reciprocal definition of spatial elements and spatial syntaxes

This paper presents a study of the relationship between city elements, as defined byLynch, and the spatial descriptors commonly used in space syntax research, leadingto a proposed relationship between the hitherto unrelated concepts of intelligibilityand imageability. The paper starts by demonstrating how each of Lynch? s five cityelements (the node, path, district, edge and landmark) may be redefined using aselection of spatial notations, primarily the axial line and the isovist. Furthermore,by precisely defining the relationship between the axial line and the isovist, it can beshown that all of Lynch? s elements may be redefined using a single, coherent familyof tightly-related spatial entities. A case study of Boston, circa 1950, is used to testan application of these redefinitions and the relationships between the various spatialdescriptors and Lynch? s elements. In turn, this leads to a hypothesis concerning therelationship between the concepts of intelligibility and imageabilty, concepts thatwere previously considered to be independent. Finally, the paper concludes bybuilding upon the relationship between intelligibility and imageabilty to concludethat this relationship provides strong evidence for an underlying cognitive basis tospace syntax.
MHCflurry: open-source class I MHC binding affinity prediction

Machine learning prediction of the interaction between major histocompatibility complex I (MHC I) proteins and their small peptide ligands is important for vaccine design and other applications in adaptive immunity. We describe and benchmark a new open-source MHC I binding prediction package, MHCflurry. The software is a collection of allele-specific binding predictors incorporating a novel neural network architecture and adhering to software development best practices. MHCflurry outperformed the standard predictors NetMHC 4.0 and NetMHCpan 3.0 on a benchmark of mass spec-identified MHC ligands and showed competitive accuracy on a benchmark of affinity measurements. The accuracy improvement was due to substantially better prediction of non-9-mer peptide ligands, which offset a narrowly lower accuracy on 9-mers. MHCflurry was on average 8.6X faster than NetMHC and 44X faster than NetMHCpan; performance is further increased when a graphics processing unit (GPU) is available. MHCflurry is freely available to use, retrain, or extend, includes Python library and command line interfaces, and may be installed using standard package managers.