Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comprehensive Algorithm for Management of Neuropathic Pain

Abstract Background The objective of this review was to merge current treatment guidelines and best practice recommendations for management of neuropathic pain into a comprehensive algorithm for primary physicians. The algorithm covers assessment, multidisciplinary conservative care, nonopioid pharmacological management, interventional therapies, neurostimulation, low-dose opioid treatment, and targeted drug delivery therapy. Methods Available literature was identified through a search of the US National Library of Medicine’s Medline database, PubMed.gov. References from identified published articles also were reviewed for relevant citations. Results The algorithm provides a comprehensive treatment pathway from assessment to the provision of first- through sixth-line therapies for primary care physicians. Clear indicators for progression of therapy from firstline to sixth-line are provided. Multidisciplinary conservative care and nonopioid medications (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances) are recommended as firstline therapy; combination therapy (firstline medications) and tramadol and tapentadol are recommended as secondline; serotonin-specific reuptake inhibitors/anticonvulsants/NMDA antagonists and interventional therapies as third-line; neurostimulation as a fourth-line treatment; low-dose opioids (no greater than 90 morphine equivalent units) are fifth-line; and finally, targeted drug delivery is the last-line therapy for patients with refractory pain. Conclusions The presented treatment algorithm provides clear-cut tools for the assessment and treatment of neuropathic pain based on international guidelines, published data, and best practice recommendations. It defines the benefits and limitations of the current treatments at our disposal. Additionally, it provides an easy-to-follow visual guide of the recommended steps in the algorithm for primary care and family practitioners to utilize.
Copper Transport and Disease: What Can We Learn from Organoids?

Many metals have biological functions and play important roles in human health. Copper (Cu) is an essential metal that supports normal cellular physiology. Significant research efforts have focused on identifying the molecules and pathways involved in dietary Cu uptake in the digestive tract. The lack of an adequate in vitro model for assessing Cu transport processes in the gut has led to contradictory data and gaps in our understanding of the mechanisms involved in dietary Cu acquisition. The recent development of organoid technology has provided a tractable model system for assessing the detailed mechanistic processes involved in Cu utilization and transport in the context of nutrition. Enteroid (intestinal epithelial organoid)-based studies have identified new links between intestinal Cu metabolism and dietary fat processing. Evidence for a metabolic coupling between the dietary uptake of Cu and uptake of fat (which were previously thought to be independent) is a new and exciting finding that highlights the utility of these three-dimensional primary culture systems. This review has three goals: (a) to critically discuss the roles of key Cu transport enzymes in dietary Cu uptake; (b) to assess the use, utility, and limitations of organoid technology in research into nutritional Cu transport and Cu-based diseases; and (c) to highlight emerging connections between nutritional Cu homeostasis and fat metabolism. Expected final online publication date for the Annual Review of Nutrition Volume 39 is August 21, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Broadband high-gain Linearly Tapered Slot Antenna with outside corrugations

This paper presents a high-gain antipodal linearly tapered slot antenna (LTSA) combined with substrate integrated waveguide (SIW) technique for Ku-band applications. The effects of periodic corrugation on the radiating elements are thoroughly investigated to optimize antenna performance. The periodic corrugation contributes to higher gain as well as and lower sidelobe level. The proposed antenna demonstrates broadband performance for frequency ranges from 13GHz to over 17GHz with gain of 16dBi and relatively low cross-polarization levels of less than -25dB. The 3-dB beam-widths of 36° in the H-plane and 22° in the E-plane have been obtained.
Joy in Work and Reducing Nurse Burnout: From Triple Aim to Quadruple Aim.

DOI: https://doi.org/10.4037/aacnacc2019833 I 2007 the Institute for Healthcare Improvement presented what is now called the “Triple Aim” as a framework that describes an approach for optimizing health system performance. The institute has indicated that new designs are needed to simultaneously pursue the 3 dimensions of the Triple Aim: (1) improving the patient experience of care (including quality and satisfaction), (2) improving the health of populations, and (3) reducing the per capita cost of health care.1 The primary focus of the Triple Aim is patient care. Patient care is widely accepted in the United States as an important agenda, but the Triple Aim also has 2 secondary goals: improving the patient experience and reducing costs.2 This article addresses the health care provider’s work environment, the Triple Aim, and the evolution of what is known as the “Quadruple Aim. ” Healthy work environments are related to the goals of the Triple Aim. Improvement of the work environment provides an opportunity to promote joy in the workplace. Interventions to improve the work environment of health care providers are consistent with the Healthy Work Environment standards of the American Association of Critical-Care Nurses (AACN). 3
Specific P300 features in patients with cycloid psychosis

In previous studies, low amplitudes and asymmetrical topography with right‐sided peaks of the P300‐evoked response have been repeatedly described in schizophrenic patients. A total of 18 patients with cycloid psychosis fulfilling the criteria of Perris and Brockington and 18 controls were investigated with a standard auditory odd‐ball paradigm and multichannel‐evoked potential recordings. Patients had normal P300 topographies and latencies but significantly higher amplitudes than controls. Higher than normal P300 amplitudes have not been described in any other psychiatric disorder until now, and indicate an enhanced level of arousal. Future studies are expected to shed light on the question of whether high P300 amplitudes are transitory sequelae of the acute psychotic episode or a trait of cycloid psychosis.
SOX2 is required for inner ear growth and cochlear nonsensory formation before sensory development

ABSTRACT The transcription factor sex determining region Y-box 2 (SOX2) is required for the formation of hair cells and supporting cells in the inner ear and is a widely used sensory marker. Paradoxically, we demonstrate via fate mapping that, initially, SOX2 primarily marks nonsensory progenitors in the mouse cochlea, and is not specific to all sensory regions until late otic vesicle stages. SOX2 fate mapping reveals an apical-to-basal gradient of SOX2 expression in the sensory region of the cochlea, reflecting the pattern of cell cycle exit. To understand SOX2 function, we undertook a timed-deletion approach, revealing that early loss of SOX2 severely impaired morphological development of the ear, whereas later deletions resulted in sensory disruptions. During otocyst stages, SOX2 shifted dramatically from a lateral to medial domain over 24-48 h, reflecting the nonsensory-to-sensory switch observed by fate mapping. Early loss or gain of SOX2 function led to changes in otic epithelial volume and progenitor proliferation, impacting growth and morphological development of the ear. Our study demonstrates a novel role for SOX2 in early otic morphological development, and provides insights into the temporal and spatial patterns of sensory specification in the inner ear. Summary: The transcription factor SOX2 has a novel early role in promoting progenitor proliferation and in the growth and morphogenesis of the otocyst before its sensory-specific function during inner ear development.
Sunblocks: Mechanisms of action

Sunscreening agents act either as ultraviolet (UV) radiation absorbers or as physical agents which reflect and scatter radiation. This brief review summarizes current concepts of how the so-called reflectant mineral or pigment sunblocks work, and the principles underlying their efficacy in screening visible and UV radiation. Sunscreens first began to be used in the 1920s when salicylates were found to reduce the sunburning effects of the sun. In the 1930s, petrolatum was also in use, and in widespread use by the 1940s, for arm troops stationed in the tropics (1). Para-amino-benzoic acid (PABA) then became the commonest sunscreen followed by a wide variety of other organic chemicals up to the present day. Mineral compounds were first used in cosmetics such as foundations, powders, eyeshadows, pencils and as whitening agents (initially zinc coxide (ZnO), superseded by titanium dioxide (TiO2) because of its superior whitening properties) in textiles, pottery, paints, also as camouflage compounds. TiO2 was reported to be a sunscreening agent in 1952 (2). The ability of a mineral to block light may be determined by several physical properties: The refractive index, size of the particles, dispersion in the base and film thickness. The reflectant property of a sunblock is determined by the formula Np/Nm, where Np is the refractive index of the pigment in question, and Nm is the refractive index of the adjacent medium, air in this circumstance. It is, of course, impossible to alter the refractive index of air, but by choosing a pigment
Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor

Key Points Nicotine can attenuate joint inflammation and pain in experimental OA via α7-nAChRs. Nicotine inhibits MMP-9 production by macrophages through the PI3K/Akt/NF-κB pathway. Osteoarthritis (OA) is a degenerative joint disease that causes chronic disability among the elderly. Despite recent advances in symptomatic management of OA by pharmacological and surgical approaches, there remains a lack of optimal approaches to manage inflammation in the joints, which causes cartilage degradation and pain. In this study, we investigated the efficacy and underlying mechanisms of nicotine exposure in attenuating joint inflammation, cartilage degradation, and pain in a mouse model of OA. A mouse model of OA was induced by injection of monosodium iodoacetate into the knee joint. Cell culture models were also used to study the efficacy and underlying mechanisms of nicotine treatment in attenuating symptoms of OA. Nicotine treatment reduced mechanical allodynia, cartilage degradation, and the upregulation of matrix metalloproteinase-9 (MMP-9), a hallmark of joint inflammation in OA, in mice treated with monosodium iodoacetate. The effects of nicotine were abolished by the selective α7 nicotinic acetylcholine receptor (nAChR) blocker, methyllycaconitine . In RAW264.7 cells and murine primary bone marrow–derived macrophages, nicotine significantly inhibited MMP-9 production induced by LPS. In addition, nicotine significantly enhanced PI3K/Akt and inhibited NF-κB translocation from the cytosol to the nucleus in an α7-nAChR–dependent manner, suggesting that nicotine acts on α7-nAChRs to inhibit MMP-9 production by macrophages through modulation of the PI3K/Akt–NF-κB pathway. Our results provide novel evidence that nicotine can attenuate joint inflammation and pain in experimental OA via α7-nAChRs. α7-nAChR could thus serve as a highly promising target to manage joint inflammation and pain in OA.
Design and Evaluation of Sensor Housing for Boundary Layer Profiling Using Multirotors

Traditional configurations for mounting Temperature–Humidity (TH) sensors on multirotor Unmanned Aerial Systems (UASs) often suffer from insufficient radiation shielding, exposure to mixed and turbulent air from propellers, and inconsistent aspiration while situated in the wake of the UAS. Descent profiles using traditional methods are unreliable (when compared to an ascent profile) due to the turbulent mixing of air by the UAS while descending into that flow field. Consequently, atmospheric boundary layer profiles that rely on such configurations are bias-prone and unreliable in certain flight patterns (such as descent). This article describes and evaluates a novel sensor housing designed to shield airborne sensors from artificial heat sources and artificial wet-bulbing while pulling air from outside the rotor wash influence. The housing is mounted above the propellers to exploit the rotor-induced pressure deficits that passively induce a high-speed laminar airflow to aspirate the sensor consistently. Our design is modular, accommodates a variety of other sensors, and would be compatible with a wide range of commercially available multirotors. Extensive flight tests conducted at altitudes up to 500 m Above Ground Level (AGL) show that the housing facilitates reliable measurements of the boundary layer phenomena and is invariant in orientation to the ambient wind, even at high vertical/horizontal speeds (up to 5 m/s) for the UAS. A low standard deviation of errors shows a good agreement between the ascent and descent profiles and proves our unique design is reliable for various UAS missions.
Robustification of input redundant feedback systems using robust actuator weighting in the control allocation problem

In this article, a new methodology for robust actuator weighting in the control allocation (CA) problem of input redundant feedback systems is addressed. The methodology is based on the control structural properties of the plant which were previously used for control configuration selection. Robust performance (RP) measures including H ∞ norm and structured singular value of the closed-loop system are used in this article. The capability of the approach is proven with application to lateral dynamics control of the vehicle over-actuated with front and rear steering systems. Employing the RP measures, it is concluded that the vehicle feedback control with front steering angles gives superior RP properties in comparison with the feedback loop of the rear steering angles. Based on these results, the penalty weightings in the cost function of the CA unit are determined. Simulation results based on nonlinear seven degrees of freedom vehicle handling model show that the selection of penalty weightings in the CA unit based on the RP properties of the control inputs (front and rear steering angles) improves the RP of the closed-loop.
Innovative MRI Techniques in Neuroimaging Approaches for Cerebrovascular Diseases and Vascular Cognitive Impairment

Cognitive impairment and dementia are recognized as major threats to public health. Many studies have shown the important role played by challenges to the cerebral vasculature and the neurovascular unit. To investigate the structural and functional characteristics of the brain, MRI has proven an invaluable tool for visualizing the internal organs of patients and analyzing the parameters related to neuronal activation and blood flow in vivo. Different strategies of imaging can be combined to obtain various parameters: (i) measures of cortical and subcortical structures (cortical thickness, subcortical structures volume); (ii) evaluation of microstructural characteristics of the white matter (fractional anisotropy, mean diffusivity); (iii) neuronal activation and synchronicity to identify functional networks across different regions (functional connectivity between specific regions, graph measures of specific nodes); and (iv) structure of the cerebral vasculature and its efficacy in irrorating the brain (main vessel diameter, cerebral perfusion). The high amount of data obtainable from multi-modal sources calls for methods of advanced analysis, like machine-learning algorithms that allow the discrimination of the most informative features, to comprehensively characterize the cerebrovascular network into specific and sensitive biomarkers. By using the same techniques of human imaging in pre-clinical research, we can also investigate the mechanisms underlying the pathophysiological alterations identified in patients by imaging, with the chance of looking for molecular mechanisms to recover the pathology or hamper its progression.
Electrochemical Detection of Ultratrace Lead Ion through Attaching and Detaching DNA Aptamer from Electrochemically Reduced Graphene Oxide Electrode

This paper describes a simple strategy for the ultratrace level detection of Pb2+ ion based on G-quadruplex DNA and an electrochemically reduced graphene oxide (ERGO) electrode. First, ERGO was formed on a glassy carbon electrode (GCE) by the reduction of graphene oxide (GO) using cyclic voltammetry. Subsequently, a methylene blue (MB)-tagged, guanine-rich DNA aptamer (Apt) was attached to the surface of ERGO via π-π interaction, leading to the Apt-modified ERGO electrode. The presence of Pb2+ could generate the folding of Apt to a G-quadruplex structure. The formation of G-quadruplex resulted in detaching the Apt from the ERGO/GCE, leading to a change in redox current of the MB tag. Electrochemical measurements showed the proposed sensor had an exceptional sensitivity for Pb2+ with a linear range from 10−15 to 10−9 M and a detection limit of 0.51 fM. The sensor also exhibited high selectivity for Pb2+, as well as many other advantages, such as stability, reproducibility, regeneration, as well as simple fabrication and operation processes.
Method to measure the mismatch between target and achieved received dose intensity of chemotherapy in cancer trials: a retrospective analysis of the MRC BO06 trial in osteosarcoma

Objectives In cancer studies, the target received dose intensity (tRDI) for any regimen, the intended dose and time for the regimen, is commonly taken as a proxy for achieved RDI (aRDI), the actual individual dose and time for the regimen. Evaluating tRDI/aRDI mismatches is crucial to assess study results whenever patients are stratified on allocated regimen. The manuscript develops a novel methodology to highlight and evaluate tRDI/aRDI mismatches. Design Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931). Setting Population-based study but proposed methodology can be applied to other trial designs. Participants A total of 497 patients with resectable high-grade osteosarcoma, of which 19 were excluded because chemotherapy was not started or the estimated dose was abnormally high (>1.25 × prescribed dose). Intervention(s) Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules: every 3 weeks in regimen-C and every 2 weeks in regimen-DI. Primary and secondary outcome measures tRDI distribution was measured across groups of patients derived from k-means clustering of treatment data. K-means creates groups of patients who are aRDI-homogeneous. The main outcome is the proportion of tRDI values in groups of homogeneous aRDI. Results For nearly half of the patients, there is a mismatch between tRDI and aRDI; for 21%, aRDI was closer to the tRDI of the other regimen. Conclusions For MRC BO06, tRDI did not predict well aRDI. The manuscript offers an original procedure to highlight the presence of and quantify tRDI/aRDI mismatches. Caution is required to interpret the effect of chemotherapy-regimen intensification on survival outcome at an individual level where such a mismatch is present. The study relevance lies in the use of individual realisation of the intended treatment, which depends on individual delays and/or dose reductions reported throughout the treatment. Trial registration number ISRCTN86294690.
NLRP6 Deficiency in CD4 T Cells Decreases T Cell Survival Associated with Increased Cell Death

Key Points The differentiation of naive T cells into Th1 cells induces the expression of Nlrp6. The expression of Nlrp6 by Th1 cells depends on the microbiota. Nlrp6 deficiency in T cells activates caspase-1 associated with cell death. The nucleotide-binding oligomerization domain (NOD)-like receptors belong to the family of pattern recognition receptors (PRRs). NOD-like receptors play a role in regulation of innate immune response by recognition of both pathogen-associated molecular patterns that are engulfed during phagocytic process and danger-associated molecular patterns that are mainly byproducts of cell stress mediated response. NOD-like family pyrin domain containing 6 (NLRP6) is one of the 14 pyrin domain–containing receptors. NLRP6 is highly expressed by epithelial and goblet cells to regulate epithelial renewal and mucus production in mice and humans, but its function in T cells is rather unknown. Increased caspase-1 activation and cell death were observed in mouse Nlrp6–deficient T cells following adoptive transfer into Rag2-deficient mice, indicating that Nlrp6 deficiency in CD4+ T cells led to decreased survival. Visual Abstract
Combined laser speckle imaging and fluorescent intravital microscopy for monitoring acute vascular permeability reaction

Abstract. Optical clearing agents (OCAs) and many chemicals are widely used in functional diagnosis of skin tissues. Numerous studies are associated with the transcutaneous diffusion of OCA in epidermal, dermal, and hypodermal tissues, which results in changing their optical properties. In addition, an objective approach that is suitable for screening the influence of utilized OCA, as well as various chemical agents, synthetics, and nanomaterials, on blood and lymph flows is highly desirable. In our study, a highly sensitive laser speckle imaging (LSI) system and fluorescent intravital microscopy (FIM) were used team-wise to inspect the acute skin vascular permeability reaction in mouse ear during the local application of OCA on the skin surface. Fluorescent contrast material administrated intravenously was used for quantitatively assessing the intensity of vascular permeability reaction and the strength of skin irritation. The obtained results suggest that a combined use of LSI and FIM is highly effective for monitoring the cutaneous vascular permeability reaction, with great potential for assessment of allergic reactions of skin in response to interactions with chemical substances.
In Vitro and In Vivo Effectiveness of Carvacrol, Thymol and Linalool against Leishmania infantum

Background: One of the most important causative agents of visceral leishmaniasis (VL) is Leishmania infantum, which is mainly spread by Phlebotomus and Lutzomyia sandflies in the Old and New World, respectively. Novel and effective drugs to manage this neglected vector-borne disease are urgently required. In this study, we evaluated the toxicity of carvacrol, thymol and linalool, three common essential oil constituents, on amastigotes and promastigotes of L. infantum. Methods: in vitro experiments were performed by 24 h MTT assay. Carvacrol, thymol and linalool at concentrations ranging from 1.3 to 10 μg/mL were tested on promastigotes of L. infantum. For in vivo test, two groups of hamsters (Mesocricetus auratus) received 100 mg/kg of body weight/day of carvacrol and thymol as intraperitoneal injection on day 7 post-infection, followed by a 48 h later injection. The third group was treated with the glucantime as standard drug (500 mg/kg) and the last group (control) just received normal saline. On the 16th day, the number of parasites and histopathological changes in liver and spleen were investigated. Results: 24 h MTT assay showed promising antileishmanial activity of thymol and carvacrol, with IC50 values of 7.2 (48 μM) and 9.8 μg/mL (65 μM), respectively. Linalool at all concentrations did not affect L. infantum promastigote viability. In vivo toxicity data of carvacrol and thymol showed that the former at 100 mg/kg was the safest and most effective treatment with little side effects on the liver. Conclusions: Overall, thymol and carvacrol are highly promising candidates for the development of effective and safe drugs in the fight against VL.