Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening Chemicals for Receptor‐Mediated Toxicological and Pharmacological Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow

Assessing compounds for their pharmacological and toxicological properties is of great importance for industry and regulatory agencies. In this study an approach using open source software and open access databases to build screening tools for receptor‐mediated effects is presented. The retinoic acid receptor (RAR), as a pharmacologically and toxicologically relevant target, was chosen for this study. RAR agonists are used in the treatment of a number of dermal conditions and specific types of cancer, such as acute promyelocytic leukemia. However, when administered chronically, there is strong evidence that RAR agonists cause hepatosteatosis and liver injury. After compiling information on ligand‐protein‐interactions, common substructures and physico‐chemical properties of ligands were identified manually and coded into SMARTS strings. Based on these SMARTS strings and calculated physico‐chemical features, a rule‐based screening workflow was built within the KNIME platform. The workflow was evaluated on two datasets: one with RAR agonists exclusively and another large, chemically diverse dataset containing only a few RAR agonists. Possible modifications and applications of screening workflows, dependent on their purpose, are presented.
Transcranial Direct Current Stimulation to the Right Temporoparietal Junction for Social Functioning in Autism Spectrum Disorder: A Case Report

Objectives While there is evidence of improved social functioning after applying transcranial direct current stimulation (tDCS) at the right temporoparietal junction (rTPJ) in individuals who are healthy, no current studies have investigated the use of tDCS at the rTPJ to improve social functioning in individuals with autism spectrum disorder (ASD). This case investigates the use of tDCS applied to the rTPJ to target social functioning in a high-functioning adult with ASD. Methods The authors present a case of an 18-year old patient with ASD treated successfully with tDCS; 1.5 mA of tDCS was applied once a day for 30 minutes for 8 consecutive days with the anode electrode over rTPJ (CP6 in the 10/10 electroencephalogram system) and the cathode electrode placed on the ipsilateral deltoid. Behavioral outcome was assessed using the Autism Treatment Evaluation Checklist prior to tDCS, after the final tDCS session, and at 2 months after tDCS. An additional, informal follow-up was also made 1 year after tDCS. Results Autism Treatment Evaluation Checklist showed substantial improvement in social functioning from baseline to post-tDCS, which was maintained at 2 months. The patient also reported lessened feelings of anger and frustration over social disappointments. Informal follow-up 1 year after stimulation indicates that the patient continues to maintain many improvements. Conclusions Anodal tDCS to the rTPJ may represent an effective treatment for improving social functioning in ASD, with a larger clinical trial needed to validate this effect.
Green Tea Polyphenols Modulate Colonic Microbiota Diversity and Lipid Metabolism in High-Fat Diet Treated HFA Mice.

There is an increasing interest in the effect of dietary polyphenols on the intestinal microbiota and the possible associations between this effect and the development of obesity. However, limited information is available on how these polyphenols affect the gut microbiota and lipid metabolism. The co-action of a high-fat diet (HFD) and tea polyphenol (TP) on gut microbiota and lipid metabolism using a human flora-associated (HFA) C57BL/6J mice model is studied. TP reduced serum total cholesterol, triglyceride, low density lipoprotein, glucose (GLU) and insulin (INS) levels of HFD mice in a dose-dependent manner (P < 0.01). TP also significantly increased acetic acid and butyric acid levels in HFA mice. 16S rRNA V3 region Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) profiles showed that HFD mice had significantly reduced microbial diversity. This reduction could be alleviated by TP, with a significant increase in the richness and diversity of colonic microbiota in the high-fat diet with 0.2% TP (TPM) and high-fat diet with 0.05% TP (TPL) groups (P < 0.05). 454 pyrosequencing analysis showed that the HFD group had a significant increase in the Bacteroidetes to Firmicutes (F/B) ratio (P < 0.001), which could effectively be reversed by TP. The results showed that the changes in composition and diversity of colonic microbiota by TP administration suppressed the host body weight and blood lipid increase in high-fat diet HFA mice. PRACTICAL APPLICATION A high fat diet significantly impacted gut microbiota composition and lipid metabolism in human flora-associated mice, which were largely ameliorated by tea polyphenol (TP). Therefore, TPs may be effectively used in controlling or treating obesity, hyperlipidemia and other related metabolic diseases.
The association between physical activity and dietary inflammatory index on mortality risk in U.S. adults

ABSTRACT Objective: Both diet and physical activity have been shown to be associated with reduced risk for mortality. The current study examined the individual and combined effects of the inflammatory quality of diet and physical activity levels on mortality risk. Methods: Data from the 1999–2004 National Health and Nutrition Examination Survey were used (N = 10,610 adults 20–85 years). Participants were followed through 2011, entailing a median follow-up time of 9.6 yrs. Dietary patterns were assessed using the Dietary Inflammatory Index (DII®), with a higher score indicative of greater diet-related inflammation. Habitual physical activity was assessed via a 30-day recall of leisure-time physical activity as well as objectively via up to seven days of accelerometry assessment. Four lifestyle groups were created: 1) unfavorable DII and inactive (referent); 2) unfavorable DII and active; 3) favorable DII and inactive; and 4) favorable DII and active. Results: Those who had a low DII score (favorable) and who self-reported being active had a 39% reduced hazard of all-cause mortality (HR = 0.61; 95% CI: 0.49–0.76) when compared to those with a higher DII and were inactive. Results based on accelerometer-assessed physical activity indicate a 65% reduced hazard (HR = 0.35; 95% CI: 0.17–0.74). DII and physical activity also were individually associated with mortality in the expected direction. Specifically, DII was positively associated (HR = 1.08; 95% CI: 1.04–1.13) and physical activity inversely associated (HR = 0.97; 95% CI: 0.94–0.99) with all-cause mortality risk. Conclusion: The combination of consuming a more anti-inflammatory diet and having adequate levels of physical activity is associated with a reduced risk of mortality. Additional replicative work is warranted.
Real-time relief mapping on arbitrary polygonal surfaces

This paper presents a technique for mapping relief textures onto arbitrary polygonal models in real time. In this approach, the mapping of the relief data is done in tangent space. As a result, it can be applied to polygonal representations of curved surfaces producing correct self-occlusions, interpenetrations, shadows and per-pixel lighting effects. The approach can be used to consistently add surface details to geometric models undergoing deformations, such as in the case of animated characters commonly found in games. The technique uses an inverse formulation (i.e., pixel driven) based on an efficient ray-height-field intersection algorithm implemented on the GPU. It supports extreme close-up views of the surfaces, mip mapping and anisotropic texture filtering. Also, contrary to high-dimensional representations of surface details, the low memory requirements of the proposed technique do not restrict its use to tiled textures.
Gene expression profile in human induced pluripotent stem cells: Chondrogenic differentiation in vitro, part B

The development of human induced pluripotent stem cells (hiPSCs) is considered a turning point in tissue engineering. However, more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte-like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with HC-402-05a cells or supplemented with transforming growth factor β3 (TGF-β3), and to assess the relative utility of the most commonly-used chondrogenic markers as indicators of cell differentiation. These issues are relevant with regard to the use of human fibroblasts in the reprogramming process to obtain hiPSCs. Human fibroblasts are derived from mesoderm and thus share a wide range of properties with chondrocytes, which originate from the mesenchyme. The hiPSCs were obtained from human primary dermal fibroblasts during a reprogramming process. Two methods, both involving embryoid bodies (EB), were used to obtain chondrocytes from the hiPSCs: EBs formed in the presence of a chondrogenic medium with TGF-β3 (10 ng/ml) and EBs formed in a medium conditioned with growth factors from HC-402-05a cells. Based on reverse transcription-quantitative polymerase chain reaction analysis, the results demonstrated that hiPSCs are capable of effective chondrogenic differentiation, with the cells obtained in the HC-402-05a medium presenting with morphological features and markers characteristic of mature human chondrocytes. In contrast, cells differentiated in the presence of TGF-β3 presented with certain undesirable hypertrophic characteristics. Several genes, most notably runt-related transcription factor 2, transforming growth factor β2 and transforming growth factor β3, were good markers of advanced and late hiPSC chondrogenic differentiation, whereas transforming growth factor β3I, II, III receptors and bone morphogenetic protein-2, bone morphogenetic protein-4 and growth differentiation factor 5 were less valuable. These findings provide valuable data on the use of stem cells in cartilage tissue regeneration.
Natural options for management of melasma, a review

ABSTRACT A blemish free, even-toned skin is universally associated with healthy skin. This reasoning makes people desire to have a flawless skin. Melanin is a naturally occurring pigment in humans. This pigment is responsible for skin, hair, and eye color, therefore determines our race and phenotypic appearance. On darker skin types, it is common that melanin production processes malfunctions. These malfunctions often lead to overproduction and secretion of melanin. As a result, unwanted pigmentary problems such melasma occur. Due to unknown etiology and its recurrence in nature, melasma is challenging to treat. The current available melasma treatment options often produce undesired side effects and suboptimum results. First-line topical treatments usually involve hydroquinone or topical steroids. Apart from the irritant reactions, this treatment mode is not suitable for all skin types. Skin care specialists are in search of an effective long-term cosmetics and cosmeceuticals to address hypermelanosis problems. Understanding of naturally occurring depigmenting agents provides an opportunity for more effective ways to manage melasma in all skin types. This review considers the benefits of naturally occurring ingredients which could help address skin pigmentation problems and broaden the choice for skin-lightening treatments.
Observer design for lipschitz nonlinear systems with time-varying output and state delays

This research paper deals with a novel delay-range-dependent approach for observer design for systems with time-varying delay in the state variables and the output measurement vector. Lyapunov Karasovskii (LK) functional, Jensen's inequality and linear matrix inequality(LMI) tools are employed to derive the stability conditions ensuring the state estimation error to asymptotically converge to the origin. Further, as particular cases of proposed design methodology, delay-range-dependent design conditions are separately deduced for systems with state delays or output delays. Numerical example is simulated to validate the efficiency of the derived results.
High-performance waveguide-integrated germanium PIN photodiodes for optical communication applications [Invited]

This paper reports on high-performance waveguide-integrated germanium photodiodes for optical communications applications. 200 mm wafers and production tools were used to fabricate the devices. Yields over 97% were obtained for three different compact photodiodes (10×10 μm and intrinsic region width of 0.5, 0.7, and 1 μm) within the same batch of three wafers. Those photodiodes exhibit low dark currents under reverse bias with median values of 74, 62, and 61 nA for intrinsic widths of 0.5, 0.7, and 1 μm, respectively, over a full wafer. Responsivities up to 0.78 A/W at 1550 nm and zero bias were measured. Zero bias operation is possible for 25 and 40 Gbps with receiver sensitivity estimated to −13.9 and −12.3 dBm, respectively.
Improved Patient Education Facilitates Adherence to Preoperative Fasting Guidelines

Preoperative fasting is recognised as an important factor in perioperative patient care. Implementation of guidelines on preoperative fasting remains sub-optimal. We audited perioperative fasting in a district general hospital, implemented changes to the preoperative information leaflet and improved fasting practices. The manner in which information is presented to patients impacts behavior and adherence to recommendations. Improving this domain of clinical practice requires thorough and conscious effort and repeated reassessment.
Study on the preparation and properties of aligned carbon nanotubes/polylactide composite fibers

The oriented carbon nanotubes (CNTs)/polylactic acid (PLA) composite fibers was prepared by the modified electrospinning technology, and characterized by Raman, X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetric (TG)/differential scanning calorimetric (DSC) analyses, respectively. Results showed that functionalized MWNTs have obvious orientation along the fiber axial in the interior of the electrospun PLA fibers, and improved the crystallization degree of PLA in the composite fibers due to the heterogeneous nucleation effect. The influences of polycaprolactone-functionalized multiwalled carbon nanotubes (MWNTs-PCL) on the performances of PLA fibers were studied. The crystallization region inside the MWNTs–PCL/PLA composite fibers was enlarged by increasing the MWNTs-PCL content. As a result, enhanced crystallization temperature was obtained. Moreover, a small amount of MWNTs-PCL (0.5%) improved the thermal stability of PLA matrix, while excess MWNTs-PCL (3.0%) induced the decrease of the thermal stability of PLA resin due to the agglomeration of MWNTs-PCL. POLYM. COMPOS. , 2012. © 2012 Society of Plastics Engineers
Bubble removal in rotational molding

Closed form solutions have been obtained for bubble dissolution in typical polymer melts encountered in rotational molding. The solutions are in excellent agreement with experimental data available in the literature. Using these solutions, it is shown that under typical rotational molding conditions the polymer melts may be almost saturated. As a result, bubble shrinkage occurs over long periods. Depending on the degree of saturation, surface tension may contribute substantially to the concentration gradient that drives bubble shrinkage. It is also shown that a pressure increase imposed on a nearly saturated polymer melt leads to a steep concentration gradient at the bubble/melt interface that can cause extremely fast bubble shrinkage. Applied to the rotational molding process, such a pressure increase can result in substantial cycle-time shortening through elimination (or reduction) of the currently used excessive heating. A further benefit may be that additional resins, which at present cannot be used because of oxidation at sustained high-temperatures, can become available to the rotational molding industry. Under the under-saturated conditions created by a pressure increase, the effect of surface tension on the rate of bubble shrinkage is negligible.
The C 32 alkane-1,15-diol as a proxy of late Quaternary riverine input in coastal margins

Abstract. The study of past sedimentary records from coastal margins allows us to reconstruct variations in terrestrial input into the marine realm and to gain insight into continental climatic variability. There are numerous organic proxies for tracing terrestrial input into marine environments but none that strictly reflect the input of river-produced organic matter. Here, we test the fractional abundance of the C32 alkane 1,15-diol relative to all 1,13- and 1,15-long-chain diols (FC32 1, 15) as a tracer of input of river-produced organic matter in the marine realm in surface and Quaternary (0–45 ka) sediments on the shelf off the Zambezi and nearby smaller rivers in the Mozambique Channel (western Indian Ocean). A Quaternary (0–22 ka) sediment record off the Nile River mouth in the eastern Mediterranean was also studied for long-chain diols. For the Mozambique Channel, surface sediments of sites most proximal to Mozambique rivers showed the highest F1, 15 − C32 (up to 10 %). The sedimentary record shows high (15–35 %) pre-Holocene F1, 15 − C32 and low (
Impact of Perturbations on Nonlinear Frequency-Division Multiplexing

Nonlinear frequency-division multiplexing (NFDM) is a communication scheme in which users’ signals are multiplexed in the nonlinear Fourier domain. The contributions of this paper are twofold. First, the achievable information rates (AIRs) of NFDM based on an integrable model of the optical fiber are summarized. For this ideal model, it is shown that the AIR of the NFDM is greater than the AIR of the wavelength-division multiplexing (WDM) for a given bandwidth and signal power, in a representative system with five users and one symbol per user. The improvement results from nonlinear signal multiplexing. Second, the impact of some of the main perturbations on NFDM are investigated, including the fiber loss, polarization effects, and the third-order dispersion. For a realistic nonideal model, it is shown that the WDM AIR with joint dual-polarization back-propagation and third-order dispersion compensation is approximately equal to the NFDM AIR with two independent single-polarization demodulations and without third-order dispersion compensation. Using a joint dual-polarization receiver and perturbations compensation is expected to increase the NFDM AIR.
Impact of Neurointensivist Co-management on the Clinical Outcomes of Patients Admitted to a Neurosurgical Intensive Care Unit

Limited data are available on improved outcomes after initiation of neurointensivist co-management in neurosurgical intensive care units (NSICUs) in Korea. We evaluated the impact of a newly appointed neurointensivist on the outcomes of neurosurgical patients admitted to an intensive care unit (ICU). This retrospective observational study involved neurosurgical patients admitted to the NSICU at Samsung Medical Center between March 2013 and May 2016. Neurointensivist co-management was initiated in October 1 2014. We compared the outcomes of neurosurgical patients before and after neurointensivist co-management. The primary outcome was ICU mortality. A total of 571 patients were admitted to the NSICU during the study period, 291 prior to the initiation of neurointensivist co-management and 280 thereafter. Intracranial hemorrhage (29.6%) and traumatic brain injury (TBI) (26.6%) were the most frequent reasons for ICU admission. TBI was the most common cause of death (39.0%). There were no significant differences in mortality rates and length of ICU stay before and after co-management. However, the rates of ICU and 30-day mortality among the TBI patients were significantly lower after compared to before initiation of neurointensivist co-management (8.5% vs. 22.9%; P = 0.014 and 11.0% vs. 27.1%; P = 0.010, respectively). Although overall outcomes were not different after neurointensivist co-management, initiation of a strategy of routine involvement of a neurointensivist significantly reduced the ICU and 30-day mortality rates of TBI patients.
Transdermal buprenorphine to switch patients from higher dose methadone to buprenorphine without severe withdrawal symptoms.

The partial opiate agonist buprenorphine was developed in the 1970s and first used as analgesic in low dosages. After the initial registration in France in 1995, it is now approved in 40 countries and can be used as a sublingual tablet in substitution treatment of opiate dependence. Buprenorphine has some advantages over methadone, such as missing evidence for QTc prolongation,1 possible alternate day dosing,2 limited respiratory depression,3 and a lower risk of overdosing.4 A transition from methadone to buprenorphine can become necessary for many reasons. There is presently no standard protocol for transition from high-dose methadone to buprenorphine. In general, a prior reduction to a dose of a maximum of 40 mg/day is recommended before methadone should be discontinued.5 Then, due to only partial agonism of buprenorphine, and its higher affinity to μ-receptors, patients have to wait for about 36–48 hours until withdrawal symptoms develop and the first dose can be given. Afterwards, buprenorphine should be increased to an adequate maintenance dosage within a few days. Prior tapering of an otherwise stable methadone dose could produce an increased relapse rate. Patient comfort also tends to be low because of withdrawal symptoms often experienced during transfer periods. The aim of this study was, therefore, to examine methods that could be used to give patients in higher dose methadone treatment the possibility to switch to buprenorphine without a prior reduction of the dose, decrease withdrawal discomfort, and keep the transfer time period as short as possible. A total of 11 subjects were enrolled in the study. All were in methadone maintenance treatment for at least 3 months with a dose between 70 mg and 100 mg and all
Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients

Background and objective Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer’s disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the ‘real-world’ arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic. Methods We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service. Results API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API. Conclusions API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment.