Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety evaluation of perampanel as monotherapy or first adjunctive therapy in patients with epilepsy

ABSTRACT Introduction There is a need for anti-seizure medications (ASMs) that are well tolerated and effective as monotherapy or first adjunctive therapy to reduce the need for adjunctive ASMs to treat newly diagnosed epilepsy, and to reduce the number of concomitant ASMs in patients with refractory epilepsy. Although the pivotal trials of perampanel evaluated its adjunctive use in patients with refractory seizures, open-label/real-world studies support its use in first/second-line settings. Areas covered This paper reviews the pharmacology, efficacy, and safety/tolerability of perampanel, focusing on its use as monotherapy or first adjunctive therapy. The safety of perampanel in special populations and its safety/tolerability compared with that of other ASMs is also discussed. Expert opinion Perampanel is a favorable candidate for initial or first adjunctive therapy due to its favorable efficacy and safety/tolerability as monotherapy and adjunctive therapy, its long half-life and ease of use, and its limited drug–drug interactions. The proposed mitigation strategies for managing the risk of serious psychiatric adverse events are appropriate patient selection, use of low doses, and slow titration. The growing body of evidence might shift current treatment strategies toward the early use of perampanel and its use at a low dose (4 mg/day).
Genetically modified (GM) late blight-resistant potato and consumer attitudes before and after a field visit

ABSTRACT Late blight, caused by Phytophthora infestans, is the most devastating disease in potato production. Here, we show full late blight resistance in a location with a genetically diverse pathogen population with the use of GM potato stacked with three resistance (R) genes over three seasons. In addition, using this field trials, we demonstrate that in-the-field intervention among consumers led to change for more favorable attitude generally toward GM crops.
Analysis of shared cognitive tasks in the application of non-invasive ventilation to patients with COPD exacerbation

ABSTRACT Interprofessional teamwork plays a key role in the uptake of evidence-based interventions, such as noninvasive ventilation (NIV) for patients with exacerbated Chronic Obstructive Pulmonary Disease (COPD). We aimed to identify the shared cognitive tasks in interprofessional teams using NIV for patients with COPD exacerbation. We used a cognitive task analysis approach (CTA) to engage nurses, rapid response team members, respiratory therapists, and physicians involved in the use of NIV to treat patients with COPD exacerbation. Clinicians participated in a semi-structured interview (n = 21) that elicited cognitions needed to treat COPD exacerbation. Three shared cognitive tasks were identified: Complete a thorough assessment, Formulate a care plan, and Continuously monitor patient status. Findings attest to the importance of having access to up-to-date information and expertise necessary to make accurate clinical inferences for patient assessment. Shared understanding of the formulated care plan among all members of the care team was important to its execution. Continuous monitoring was crucial; however, this cognitive task relied on patient assessment skills and ongoing collaboration within the clinical care team. Application of NIV for patients with COPD exacerbation may require enhancing collaboration through nontechnical skills and interprofessional training.
Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211)

PURPOSE Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RRs) and long progression-free survival (PFS). PATIENTS AND METHODS E2211 was a multicenter, randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced low-grade or intermediate-grade pancreatic NETs. Key eligibility criteria included progression within the preceding 12 months and no prior temozolomide, dimethyl-triazeno-imidazole-carboxamide or dacarbazine, capecitabine or fluorouracil. The primary end point was PFS; secondary endpoints were overall survival, RR, safety, and methylguanine methyltransferase (MGMT) by immunohistochemistry and promoter methylation. RESULTS A total of 144 patients were enrolled between April 2013 and March 2016 to temozolomide (n = 72) or capecitabine and temozolomide (n = 72); the primary analysis population included 133 eligible patients. At the scheduled interim analysis in January 2018, the median PFS was 14.4 months for temozolomide versus 22.7 months for capecitabine/temozolomide (hazard ratio = 0.58), which was sufficient to reject the null hypothesis for the primary end point (stratified log-rank P = .022). In the final analysis (May 2021), the median overall survival was 53.8 months for temozolomide and 58.7 months for capecitabine/temozolomide (hazard ratio = 0.82, P = .42). MGMT deficiency was associated with response. CONCLUSION The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced pancreatic NETs. The median PFS and RR observed with capecitabine/temozolomide are the highest reported in a randomized study for pancreatic NETs. MGMT deficiency was associated with response, and although routine MGMT testing is not recommended, it can be considered for select patients in need of objective response (ClinicalTrials.gov identifier: NCT01824875).
Multicenter, international observational study on quality of life and acceptability of a vaginal contraceptive ring containing etonogestrel/ethinylestradiol 11.00/3.474 mg over six months of use.

OBJECTIVE The current post-market study aimed at analyzing women's menstrual bleeding intensity, vaginal infections, and quality of life parameters using the contraceptive vaginal ring Ornibel®. PATIENTS AND METHODS In Germany and Spain, a multicenter study of healthy female adults (n=211) aged 18 to 45 used the vaginal ring Ornibel® for at least six months. Data collection was conducted using a patient questionnaire. The menstrual bleeding intensity was analyzed using visual analog scales (VAS). A Chi-square linear trend test assessed associations between quality-of-life parameters and continuation and recommendation of vaginal ring use. RESULTS Three out of four women experienced six menstrual bleedings during the first six months of using the vaginal ring, with a median duration of four days during the study. The use of the vaginal ring led to a significant reduction in menstrual flow intensity (from 60 VAS points to 40 VAS points, p<0.001). In the German cohort, it was shown that dysmenorrhea and unscheduled bleeding and spotting were reduced with the use of Ornibel® as well. Most women (93.7%) agreed or strongly agreed that the vaginal ring was easy to insert, and its use was rated as comfortable or very comfortable by 97.5%. Both parameters were significantly associated with the continuation of the ring (easy to insert p=0.01, feeling comfortable: p=0.002) or its recommendation (easy to insert p=0.002, feeling comfortable: p=0.002). CONCLUSIONS The observational data demonstrate that the contraceptive vaginal ring provides high acceptability and comfort. It is a well-accepted contraceptive method characterized by high efficacy and positive effects on cycle control.
On the angular distribution of IceCube high-energy events

The detection of high-energy astro-physical neutrinos of extraterrestrial origin by the IceCube neutrino observatory in Antarctica has opened a unique window to the cosmos that may help to probe both the distant Universe and our cosmic backyard. The arrival directions of these high-energy events have been interpreted as uniformly distributed on the celestial sphere. Here, we revisit the topic of the putative isotropic angular distribution of these events applying Monte Carlo techniques to investigate a possible anisotropy. A modest evidence for anisotropy is found. An excess of events appears projected towards a section of the Local Void, where the density of galaxies with radial velocities below 3000 km s–1 is rather low, suggesting that this particular group of somewhat clustered sources are located either very close to the Milky Way or perhaps beyond 40 Mpc. The results of further analyses of the subsample of southern hemisphere events favour an origin at cosmological distances with the arrival directions of the events organized in a fractal-like structure. Although a small fraction of closer sources is possible, remote hierarchical structures appear to be the main source of these very energetic neutrinos. Some of the events may have their origin at the IBEX ribbon. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Role-Related Stress and Adversity Impacting Christian Clergy Resilience: A Pan-Canadian Study

Christian clergy are at risk of experiencing the negative impacts of role-related stress and adversity, especially burnout. The findings reported in this article were derived from a Canadian mix-methods study that collected data through an online survey with 519 clerics, 13 one-on-one interviews, and interpretation panels. Adversity themes identified related to workload, expectations, isolation, and personal challenges with various subthemes for each. These findings are relevant to those providing care to clergy by providing insights into the challenges they face.
Abrupt Emergence of Pressure-Induced Superconductivity of 34 K in SrFe2As2: A Resistivity Study under Pressure

We report resistivity measurement under pressure in single crystals of SrFe 2 As 2 , which is one of the parent materials of Fe-based superconductors. The structural and antiferromagnetic (AFM) transition of T 0 = 198 K at ambient pressure is suppressed under pressure, and the ordered phase disappears above P c ∼3.6–3.7 GPa. Superconductivity with a sharp transition appears accompanied by the suppression of the AFM state. T c exhibits a maximum of 34.1 K, which is realized close to the phase boundary at P c . This T c is the highest among those of the stoichiometric Fe-based superconductors.
Relationship between vitamin D deficiency and thrombus load in patients with ST-elevation myocardial infarction.

OBJECTIVE Clinical studies detecting the increase in thrombotic events with vitamin D deficiency note the relationship between vitamin D and thrombosis. This study aims at evaluating the relationship between serum vitamin D levels and coronary thrombus burden. PATIENTS AND METHODS We retrospectively evaluated 77 patients with ST-elevated myocardial infarction (STEMI). Serum vitamin D levels, degree of coronary thrombus, Thrombolysis in Myocardial Infarction (TIMI) frame count and the extent and severity of atherosclerosis in coronary arteries were also measured in all cases. Patients were divided into 2 groups, according to thrombus load. RESULTS The rate of vitamin D deficiency in the study population was 79.22% (< 20 ng/mL). Vitamin D levels were significantly higher in patients with a mild thrombus load than in patients with a severe thrombus load (16 vs. 13.95 p = 0.018). Gensini scores were significantly higher in patients with a severe thrombus burden than in patients with a mild thrombus burden (42 vs. 54.5 p = 0.014). There was a low negative correlation between vitamin D levels and thrombus burden classification grades (r = -0.304, p = 0.007), Cx TIMI frame counts (r = -0.402, p < 0.001), and RCA TIMI frame counts (r = -0.479, p < 0.001). There was a moderate negative correlation between serum vitamin D levels and LAD TIMI frame count (r = -0.507, p < 0.001). CONCLUSIONS The results of our study showed that low 25(OH)D3 levels are an independent predictor of high coronary artery thrombus load and post-procedural TIMI frame count increase in patients with STEMI undergoing primary percutaneous coronary intervention.
Numb regulates Tau levels and prevents neurodegeneration in tauopathy mouse models

Accumulation of the microtubule-associated protein Tau is linked to neuronal cell death in tauopathies, but how intraneuronal Tau levels are regulated in health and disease remains unclear. Here, we show that conditional inactivation of the trafficking adaptor protein Numb in retinal ganglion cells (RGCs) increases Tau levels and leads to axonal blebbing, which is followed by neuronal cell loss in aged mice. In the TauP301S mouse model of tauopathy, conditional inactivation of Numb in RGCs and spinal motoneurons accelerates neurodegeneration, and loss of Numb in motoneurons also leads to precocious hindlimb paralysis. Conversely, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels and reduces axonal blebbing in TauP301S RGCs, leading to improved electrical activity in cultured neurons and improves performance in a visually guided behavior test in vivo. These results uncover Numb as a key regulator of intracellular Tau levels and identify Numb-72 as a potential therapeutic factor for tauopathies.
Serum keratin‐18 detects hepatic inflammation and predicts progression in compensated alcohol‐associated liver disease

Alcohol‐associated liver fibrosis accumulates over decades, driven by hepatic inflammation and cell death. We investigated the diagnostic accuracy of keratin‐18 degradation, measured using serum M30 and M65 levels, and the ActiTest for hepatic inflammatory activity in patients with compensated alcohol‐associated liver disease (ALD). Furthermore, we evaluated the prognostic accuracy of markers for liver‐related events and all‐cause mortality. All findings were compared with routine liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma‐glutamyltransferase. Our prospective, biopsy‐controlled, single‐center study included 265 patients with ongoing or prior excessive alcohol intake, representing the full spectrum of compensated ALD. We defined hepatic inflammatory activity as a combined score of lobular inflammation and ballooning. For severe hepatic inflammatory activity (n = 40), we found excellent diagnostic accuracy for M30 (area under the receiver operating characteristics curve [AUROC] = 0.90), M65 (AUROC = 0.86), and AST (AUROC = 0.86). Elevated M30 (M30 > 240 U/L) had the highest positive predictive value (PPV) and specificity, significantly higher than M65, ActiTest and ALT, but not AST (M30: sensitivity = 83%, specificity = 82%, positive predictive value = 45%, negative predictive value = 95%). Patients were followed up for 1445 patient‐years. All markers, except for ALT, significantly predicted liver‐related events and all‐cause mortality. After adjusting for advanced fibrosis, drinking behavior and body mass index, M30 and M65 remained significant predictors of liver‐related events, whereas M30 and AST were significant predictors of all‐cause mortality. Conclusion: M30 and AST accurately detect severe hepatic inflammatory activity in patients with compensated ALD. M30 was the only significant predictor of both liver‐related events and all‐cause mortality after adjusting for advanced fibrosis, body mass index, and drinking behavior at inclusion.
Coffee-Derived Exosome-Like Nanoparticles: Are They the Secret Heroes?

Background: Regular coffee consumption has beneficial and preventative effects on liver and chronic neurodegenerative diseases. However, the studies performed with the ingredients found in coffee beverages have not clarified the responsible mechanisms. Exosomes are small, membrane-coated cargo packages secreted by prokaryote and eukaryote cells. Exosomes regulate intercellular communication and affect cellular metabolic activities even among different species. In this study, we aimed to isolate and characterize the edible plant-derived exosome-like nanoparticles from roasted hot coffee beverages, hypothesizing that the edible plant-derived exosome-like nanoparticles were responsible for the beneficial effects of coffee. Methods: Size exclusion chromatography and commercial kits were used for the isolation process. Efficient coffee edible plant-derived exosome-like nanoparticle fractions were determined by an ultraviolet-visible spectrophotometer. Harvested coffee edible plant-derived exosome-like nanoparticles were characterized by transmission electron microscopy. The quantification procedure was performed using a commercial kit. Coffee edible plant-derived exosome-like nanoparticles’ proliferative effects on human hepatic stellate cells and human hepatocellular carcinoma cells were studied using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Whole-exosome RNA sequencing was performed. Results: Transmission electron microscopy scanning analysis indicated round-shaped nanoparticles with sizes ranging from 40 to 100 nm. Both size exclusion chromatography and kit-isolated edible plant-derived exosome-like nanoparticle samples showed maximum absorbance at 227.5 nm in ultraviolet-visible spectrophotometer analysis. Regarding the quantitation results, kit isolation was more efficient than the size exclusion chromatography method when the harvested particle numbers were compared. An important MTT assay finding confirmed the observed beneficial effects of coffee beverages: coffee edible plant-derived exosome-like nanoparticles significantly suppressed hepatocellular carcinoma cell proliferation. As a result of sequencing, we identified 15 mature miRNAs. A MapReduce-based MicroRNA Target Prediction Method (The DIANA tools’ MR-microT algorithm) highlighted 2 genes specifically associated with the miRNAs that we obtained: KMT2C and ZNF773. Conclusion: For the first time in the literature, coffee edible plant-derived exosome-like nanoparticles were identified. These nanoparticles may have therapeutic effects on chronic liver diseases. Experimental studies, therefore, should be performed on disease models to demonstrate their efficacy.
A method for atomistic spin dynamics simulations: implementation and examples

We present a method for performing atomistic spin dynamic simulations. A comprehensive summary of all pertinent details for performing the simulations such as equations of motions, models for including temperature, methods of extracting data and numerical schemes for performing the simulations is given. The method can be applied in a first-principles mode, where all interatomic exchange is calculated self-consistently, or it can be applied with frozen parameters estimated from experiments or calculated for a fixed spin-configuration. Areas of potential application to different magnetic questions are also discussed. The method is finally applied to one situation where the macrospin model breaks down; magnetic switching in ultra strong magnetic fields.
HOW DID A MAJOR CONFINED FLARE OCCUR IN SUPER SOLAR ACTIVE REGION 12192?

We study the physical mechanism of a major X-class solar flare that occurred in the super NOAA active region (AR) 12192 using data-driven numerical magnetohydrodynamic (MHD) modeling complemented with observations. With the evolving magnetic fields observed at the solar surface as bottom boundary input, we drive an MHD system to evolve self-consistently in correspondence with the realistic coronal evolution. During a two-day time interval, the modeled coronal field has been slowly stressed by the photospheric field evolution, which gradually created a large-scale coronal current sheet, i.e., a narrow layer with intense current, in the core of the AR. The current layer was successively enhanced until it became so thin that a tether-cutting reconnection between the sheared magnetic arcades was set in, which led to a flare. The modeled reconnecting field lines and their footpoints match well the observed hot flaring loops and the flare ribbons, respectively, suggesting that the model has successfully “reproduced” the macroscopic magnetic process of the flare. In particular, with simulation, we explained why this event is a confined eruption—the consequence of the reconnection is a shared arcade instead of a newly formed flux rope. We also found a much weaker magnetic implosion effect compared to many other X-class flares.
A precision measurement of the spin structure functions g

In Experiment E155 at the Stanford Linear Accelerator Center, the spin dependent structure function g1(x, Q ) was measured for both the proton and deuteron. This was accomplished by scattering 48.3 GeV highly polarized electrons (0.813 ± 0.020) off polarized NH3 (proton) and LiD (deuteron) targets. Data were collected in March and April of 1997 using three fixed angle, momentum analyzing spectrometers centered at 2.75◦, 5.5◦, and 10.5◦. This enabled a kinematic coverage of 0.01 < x < 0.9 and 1 GeV < Q < 40 GeV. At an average Q of 5 GeV, the integrals in the measured region were ∫ 0.9 0.014 g1(x)dx = 0.119±0.002(stat.)±0.009(syst.) for the proton and 0.043± 0.003(stat.)± 0.003(syst.) for the deuteron. Using a perturbative QCD analysis which included a global data set, the results were found to be consistent with the Bjorken Sum Rule. Asymmetry measurements also were made using photoproduced hadrons. Data were collected concurrently with the g1 data. For the proton, the asymmetries were small and non-zero. The deuteron measurements were consistent with zero.
MACHO RR lyrae stars in the galactic bulge: the spatial distribution

We have analyzed a sample of 1150 type ab, and 550 type c RR Lyrae stars found in 24 bulge fields of the MACHO database. These fields cover a range in Galactocentric distances from 0.3 to 1.6 kpc. In combination with the data on the outer bulge fields of Alard (1997) and Wesselink (1987), here we present the surface density distribution of bulge RR Lyrae between 0.3 and 3 kpc. The distribution along the line of sight of the bulge RR Lyrae population was examined on the basis of the mean magnitudes, and it was shown that the bulk of the RR Lyrae population is not barred (Alcock et al. 1998). There is a hint of a bar only in the RR Lyrae of the inner fields closer to the Galactic center. The red giant clump stars in the MACHO fields, however, clearly show a barred distribution, confirming the results of previous studies (e.g. Dwek et al. 1995, Stanek et al. 1996). In the MACHO fields studied there are about 550 clump giants per RR Lyrae star. The RR Lyrae trace metal-poor stars, which are a minor component of the bulge population. The clump giants, however, should trace the bulk of the metal-rich population, foUowing underlying mass of the bulge more closely. Given the different spatial distribution, we concluded that the RR Lyrae and the clump giants trace two dif+erent populations (Alcock et al. 1998). The RR Lyrae would represent the inner extension of the Galactic halo in these fields (Minniti 1996). The observed surface distribution of RR Lyrae in the bulge fields was computed after discarding background RR Lyrae that belong to the Sgr dwarf galaxy (Alard 1996, Alcock et al. 1997). This distribution yields a power law density distribution. There is no turnover or flattening of this distribution even in the innermost fields, indicating that the RR Lyrae population is very concentrated, with core radius RC < 0.5 kpc. We also determine that the RR Lyrae surface distribution in the bulge fields is flattened, with b/a = 0.7.