Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomised test of printed educational materials about melanoma detection: Varying skin self-examination technique and visual image dose

Objective: Melanoma incidence and mortality rates continue to rise globally, making it essential for researchers to identify effective approaches to disseminating information to the public that improve key outcomes. This study compared two skin self-examination (SSE) educational strategies: the ABCDE (asymmetry, border irregularity, multiple colours, diameter greater than 6 mm and evolution over time) approach and the ugly duckling sign (UDS). Design: A randomised experiment testing different presentations of SSE techniques and visual image dose. Setting: The experiment took place at a shopping centre in the Midwest USA. Method: Participants (N = 301) participated in the study in which they viewed brochures featuring one of two SSE training methods, ABCDE or UDS, along with a low, moderate or high dosage (frequency) of visual images. Results: The brochures improved willingness to perform SSE and skin cancer knowledge across all groups, with brochures featuring the UDS increasing willingness to perform SSE as visual image dose increased. Sensitivity and specificity outcomes were similar across all groups, with a slight advantage found for displaying a moderate visual image dose visualising the ABCDE condition (sensitivity = .63, specificity = .79). Conclusions: Overall, both the ABCDE and UDS approaches demonstrated utility in improving early skin cancer detection and education. A balanced presentation of typical and atypical nevi images seems to be an important consideration when presenting visual and written information about melanoma to laypersons.
HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation

Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43, is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding protein, HuD. Novel mutants reveal that HuD is also necessary for motor axonal branch and dendrite formation. Data also revealed that both SMN and HuD affect levels of an mRNA involved in axonal growth. Moreover, expressing HuD in SMN-deficient motoneurons can rescue the motoneuron development and motor defects caused by low levels of SMN. These data support that SMN:HuD complexes are essential for normal motoneuron development and indicate that mRNA handling is a critical component of SMA.
Length scale for the onset of Fickian diffusion in supercooled liquids

The interplay between self-diffusion and excitation lines in space-time was recently studied in kinetically constrained models to explain the breakdown of the Stokes-Einstein law in supercooled liquids. Here, we further examine this interplay and its manifestation in incoherent scattering functions. In particular, we establish a dynamic length scale below which Fickian diffusion breaks down, as is observed in experiments and simulations. We describe the temperature dependence of this length scale in liquids of various fragilities, and provide analytical estimates for the van Hove and self-intermediate scattering functions.
Photon iso-effective dose for cancer treatment with mixed field radiation based on dose–response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose–response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose–response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r > 0.87 and p-values >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.
Therapeutic Potential of Natural Catechins in Antiviral Activity

Natural compounds have been discovered to be effective in many disease treatments. Among these compounds are epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), two abundant polyphenolic catechins in green tea. They have been found to be able to interfere with many disease-related biochemical processes in vitro. They are capable of suppressing inflammation, tumor growth, bacterial infection, and virus infection. Thus, EGCG and ECG have drawn great attention on the potential effects on disease prevention and treatment of carcinogenic, obesity, diabetic, and Alzheimer’s diseases. In this review, the potential of EGCG and ECG on anti-viral infection is elucidated in detail with an overview of research achievements in this field. The highlight will provide in depth knowledge on new drug discovery and contribute to the design and development of novel anti-virus agents.
Expression, Activation, and Biochemical Properties of a Novel Arabidopsis Protein Kinase1

An Arabidopsis SOS2 (salt overly sensitive 2)-like protein kinase gene, PKS6, was expressed in leaves, stems, and siliques, but not detectable in roots of adult plants; its expression in young seedlings was up-regulated by abscisic acid. To determine the biochemical properties of the PKS6 protein, we expressed the PKS6 coding sequence as a glutathione S-transferase fusion protein in Escherichia coli. The bacterially expressed glutathione S-transferase-PKS6 fusion protein was inactive in substrate phosphorylation. We have constructed constitutively active forms of PKS6 by either a deletion of its putative auto-inhibitory FISL motif (i.e. PKS6ΔF) or a substitution of threonine-178 with aspartic acid within the putative activation loop. We found that PKS6ΔF exhibited a strong preference for Mn2+ over Mg2+ as a divalent cation cofactor for kinase activity. PKS6ΔF displayed substrate specificity against three different peptide substrates and had an optimal pH of approximately 7.5 and temperature optimum of 30°C. The apparentK m values for ATP and the preferred peptide substrate p3 of PKS6ΔF were determined to be 1.7 and 28.5 μm, respectively. These results provide significant insights into the regulation and biochemical properties of the protein kinase PKS6. In addition, the constitutively active, gain-of-function kinase mutants will be invaluable for future determination of the in planta function of PKS6.
Impact of Anesthesia on the Outcome of Acute Ischemic Stroke after Endovascular Treatment with the Solitaire Stent Retriever

BACKGROUND AND PURPOSE: General anesthesia during endovascular treatment of acute ischemic stroke may have an adverse effect on outcome compared with conscious sedation. The aim of this study was to examine the impact of the type of anesthesia on the outcome of patients with acute ischemic stroke treated with the Solitaire stent retriever, accounting for confounding factors. MATERIALS AND METHODS: Four-hundred one patients with consecutive acute anterior circulation stroke treated with a Solitaire stent retriever were included in this prospective analysis. Outcome was assessed after 3 months by the modified Rankin Scale. RESULTS: One-hundred thirty-five patients (31%) underwent endovascular treatment with conscious sedation, and 266 patients (69%), with general anesthesia. Patients under general anesthesia had higher NIHSS scores on admission (17 versus 13, P < .001) and more internal carotid artery occlusions (44.6% versus 14.8%, P < .001) than patients under conscious sedation. Other baseline characteristics such as time from symptom onset to the start of endovascular treatment did not differ. Favorable outcome (mRS 0–2) was more frequent with conscious sedation (47.4% versus 32%; OR, 0.773; 95% CI, 0.646–0.925; P = .002) in univariable but not multivariable logistic regression analysis (P = .629). Mortality did not differ (P = .077). Independent predictors of outcome were age (OR, 0.95; 95% CI, 0.933–0.969; P < .001), NIHSS score (OR, 0.894; 95% CI, 0.855–0.933; P < .001), time from symptom onset to the start of endovascular treatment (OR, 0.998; 95% CI, 0.996–0.999; P = .011), diabetes mellitus (OR, 0.544; 95% CI, 0.305–0.927; P = .04), and symptomatic intracerebral hemorrhage (OR, 0.109; 95% CI, 0.028–0.428; P = .002). CONCLUSIONS: In this single-center study, the anesthetic management during stent retriever thrombectomy with general anesthesia or conscious sedation had no impact on the outcome of patients with large-vessel occlusion in the anterior circulation.
FermentedWheat Germ Extract ( Avemar ) in the Treatment of Cardiac Remodeling andMetabolic Symptoms in Rats

Avemar, a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of Avemar may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular remodeling were used in this project: the deoxycorticosterone acetate (DOCA)-salt-induced model of chronic hypertension (study I) and a high-carbohydrate/high-fat dietinduced model producing chronic symptoms of the metabolic syndrome and its associated cardiovascular complications (study II). Our results in these rat models of hypertension and diet-induced obesity show that treatment with Avemar improved cardiac function, decreased macrophage infiltration resulting in decreased collagen deposition in the ventricular myocardium, reversed an increased stiffness of the left ventricle in the diseased hearts and attenuated increased plasma malondialdehyde concentrations. In addition to the changes in the heart, Avemar reversed glucose intolerance, normalized systolic blood pressure and decreased visceral fat deposition in rats fed a high-fat/high-carbohydrate diet. In conclusion, the fermented wheat germ extract Avemar has a potential role in attenuating chronic hypertension, diabetes or metabolic syndrome-induced cardiovascular symptoms along with metabolic abnormalities such as glucose tolerance and obesity.
Clinical Experience With a Novel Glaucoma Drainage Implant

Purpose:To retrospectively evaluate the safety and efficacy of an Ahmed glaucoma valve (AGV) modified with a polyethylene shell (M4) to reduce the fibrotic reaction around the drainage plate compared with the S2 and FP7 models in patients with glaucoma. Methods:The medical records of patients who underwent implantation of the AGV FP7, S2, and M4 were reviewed. The primary outcome measure was cumulative probability of success, defined as an intraocular pressure (IOP) between 5 and 18 mm Hg and >20% reduction of IOP without loss of light perception, need for additional IOP-lowering surgical procedures, or removal of AGV. Results:Seventy-six, 38, and 40 eyes received the FP7, S2, and M4 with a mean follow-up time of 578±157, 662±186, and 504±158 days, respectively. The mean IOP was reduced from 31.0±10.6 to 13.9±5.5 mm Hg in the FP7 group, 33.5±12.1 to 15.8±8.1 mm Hg in the S2 group, and 27.0±12.0 to 15.0±4.0 mm Hg in the M4 group at 1 year (P=0.31). At 1 year, the cumulative probability of success was 70%, 66%, and 80% and at 18 months, 61%, 53%, and 52% in the FP7, S2, and M4 groups, respectively (P=0.99). Complications were similar among groups. Conclusions:No significant difference was observed between the AGV M4, FP7, and S2 at 1 year. Additional follow-up is required to determine its long-term safety profile and efficacy.
Reduced Na+ Uptake in the NaCl-Hypersensitive sos1 Mutant of Arabidopsis thaliana

sos1 is an Arabidopsis thaliana mutant with >20 times higher sensitivity toward Na+ inhibition due to a defective high-affinity potassium-uptake system. We report here that sos1 accumulates less Na+ than the wild type in response to NaCl stress. The Na+ contents in sos1 seedlings exposed to 25 mM NaCl for 2 or more d are about 43% lower than those in the wild type. When assayed at 20 mM external NaCl, sos1 seedlings pretreated with low potassium have 32% lower Na+ uptake than the wild type. However, little difference in Na+ uptake could be measured when the seedlings were not pretreated with low potassium. Low-potassium treatment was shown to induce high-affinity potassium-uptake activity in Arabidopsis seedlings. No substantial difference in Na+ efflux between sos1 and the wild type was detected. The results show that the reduced Na+ accumulation in sos1 is due to a lower Na+ influx rate. Therefore, the sos1 mutation appears to disrupt low-affinity Na+ uptake in addition to its impairment of high-affinity K+ uptake.
Muscle-Specific Splicing Factors ASD-2 and SUP-12 Cooperatively Switch Alternative Pre-mRNA Processing Patterns of the ADF/Cofilin Gene in Caenorhabditis elegans

Pre–mRNAs are often processed in complex patterns in tissue-specific manners to produce a variety of protein isoforms from single genes. However, mechanisms orchestrating the processing of the entire transcript are not well understood. Muscle-specific alternative pre–mRNA processing of the unc-60 gene in Caenorhabditis elegans, encoding two tissue-specific isoforms of ADF/cofilin with distinct biochemical properties in regulating actin organization, provides an excellent in vivo model of complex and tissue-specific pre–mRNA processing; it consists of a single first exon and two separate series of downstream exons. Here we visualize the complex muscle-specific processing pattern of the unc-60 pre–mRNA with asymmetric fluorescence reporter minigenes. By disrupting juxtaposed CUAAC repeats and UGUGUG stretch in intron 1A, we demonstrate that these elements are required for retaining intron 1A, as well as for switching the processing patterns of the entire pre–mRNA from non-muscle-type to muscle-type. Mutations in genes encoding muscle-specific RNA–binding proteins ASD-2 and SUP-12 turned the colour of the unc-60 reporter worms. ASD-2 and SUP-12 proteins specifically and cooperatively bind to CUAAC repeats and UGUGUG stretch in intron 1A, respectively, to form a ternary complex in vitro. Immunohistochemical staining and RT–PCR analyses demonstrate that ASD-2 and SUP-12 are also required for switching the processing patterns of the endogenous unc-60 pre-mRNA from UNC-60A to UNC-60B in muscles. Furthermore, systematic analyses of partially spliced RNAs reveal the actual orders of intron removal for distinct mRNA isoforms. Taken together, our results demonstrate that muscle-specific splicing factors ASD-2 and SUP-12 cooperatively promote muscle-specific processing of the unc-60 gene, and provide insight into the mechanisms of complex pre-mRNA processing; combinatorial regulation of a single splice site by two tissue-specific splicing regulators determines the binary fate of the entire transcript.
Herbal extract of Artemisia vulgaris (mugwort) induces antitumor effects in HCT-15 human colon cancer cells via autophagy induction, cell migration suppression and loss of mitochondrial membrane potential.

PURPOSE Artemisia vulgaris (A.vulgaris) belonging to family Compositae, commonly known as mugwort, has been used as a medicinal herb in Chinese traditional medicine for treatment of diseases. Studies have reported a diversity of activities for this plant which include antiseptic, antispasmodic, antigastric, anticancer and nervous system diseases. However, the anticancer activity of A.vulgaris in HCT-15 human colon cancer cells has not been scientifically validated. Therefore the present study aimed at evaluating the anticancer activity of methanolic extract of A.vulgaris against HCT-15 human colon cancer cell line. METHODS Cell cytotoxicity effects of the extract were evaluated by MTT cell viability assay, while clonogenic assay assessed the effects on cancer cell colony formation. Effects on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. In vitro wound healing assay was used to evaluate the effects on cell migration. To confirm autophagy, we evaluated the expression of several autophagy-associated proteins using Western blot assay. RESULTS Results indicated that the methanolic extract of A.vulgaris exhibited an IC50 value of 50 μg/ml and exerted its cytotoxic effects in a dose-dependent manner. Moreover, it was observed that the extract inhibits colony formation and induces autophagy dose-dependently. The underlying mechanism for the induction of autophagy was found to be ROS-mediated MMP and significant inhibition of cell migration potential of colon cancer cells at the IC50 was observed. CONCLUSION These results strongly stress that the methanolic extract may prove a source for the isolation of novel anticancer lead molecules for the management of colon cancer.
Brace-Free Rehabilitation, with Early Return to Activity, for Knees Reconstructed with a Double-Looped Semitendinosus and Gracilis Graft*†

Forty-one patients in whom operative reconstruction of a torn anterior cruciate ligament had been performed by one surgeon with use of a double-looped semitendinosus and gracilis hamstring graft were studied to determine (1) if a brace-free rehabilitation program compromised the early stability of the knee; (2) if the stability of the knee deteriorated between four months, when the patient returned to unrestricted activities, and two years; and (3) if the function of the treated knee was completely restored by four months after the operation. The graft was placed arthroscopically, without impingement by the intercondylar roof, and was fixed within the tibial tunnel to conserve the length of the graft. The stability and function of thirty-seven of the knees were assessed at four months as part of a larger prospective study. Four patients chose not to return for the four-month evaluation. The patients returned to unrestricted sports and work activities after the four-month evaluation. At two years, all forty-one patients were evaluated. At four months, after completion of the brace-free rehabilitation program, thirty-three (82 per cent) of the thirty-seven patients had an absent pivot shift and a normal Lachman test. Twenty-eight (88 per cent) of thirty-four knees had less than three millimeters of difference in laxity compared with the contralateral knee, as determined by testing at the maximum manual force with use of a KT-1000 arthrometer. Stability remained unchanged at two years, justifying the early return to vigorous activities at four months. The girth of the thigh, the extension of the knee, and the Lysholm and Gillquist score were the same at four months as at two years, verifying the success of the brace-free intensive rehabilitation program in the restoration of early function to the treated knee. However, some continued improvement was observed in the performance of the one-leg-hop for distance test between four months and two years.
New stability criteria of singular systems with time-varying delay via free-matrix-based integral inequality

ABSTRACT This paper concerns the stability problem of singular systems with time-varying delay. First, the singular system with time-varying delay is transformed into the neutral system with time-varying delay. Second, a more proper Lyapunov–Krasovskii functional (LKF) is constructed by adding some integral terms to quadratic forms. Then, to obtain less conservative conditions, the free-matrix-based integral inequality is adopted to estimate the derivative of LKF. As a result, some delay-dependent stability criteria are given in terms of linear matrix inequalities. Finally, two numerical examples are provided to demonstrate the effectiveness and superiority of the proposed method.