Miracle-dz/UniFAR-FTUs huggingface dataset:
6.2: Optimizing osmium-ruthenium films to inhibit tungsten interdiffusion

Osmium-ruthenium thin films were deposited on porous tungsten pellets, at the same time as cathode assemblies, to investigate possibilities for minimizing interdiffusion. Previous studies had identified promising film characteristics for inhibiting tungsten interdiffusion. For example, it was found that a 5W-substrate-biased film of 550 nm thickness exhibited high structural and compositional stability, and several other films exhibited promising properties as well. These films were produced and annealed, then analyzed for composition. Emission tests of M-type cathode assemblies, coated with the same candidate films, were performed to assess the degree of lifetime improvement imparted by the films to the cathodes.
Efficacy, Safety, and Pharmacokinetics of Sugammadex for the Reversal of Rocuronium-induced Neuromuscular Blockade in Elderly Patients

Background:The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18–64 yr) versus elderly adult (aged 65 yr or older) patients. Methods:This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1–3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated. Results:Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18–64 yr (adult), 62 were aged 65–74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0–2.6) min (adults) to 2.9 (2.7–3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients. Conclusion:Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.
The Resuscitation Bundle of the Surviving Sepsis Campaign Beyond Early Goal-Directed Therapy: What's Next?

To the Editor: With great interest, we read the article by Capp et al (1) who conducted an analysis of demographic and clinical factors associated with progression to septic shock among emergency department (ED) patients with sepsis. The authors performed a retrospective chart review of 1,316 patients who met the criteria for sepsis within the first 4 hours of ED arrival and reported that 8.4% of the study sample progressed to shock during the first 48 hours of hospitalization. We specifically write today to comment on the finding that women were 59% more likely to progress to septic shock than men; other factors associated with progression to shock included transient hypotension, elevated bandemia or lactate, and a history of coronary artery disease. Although ED providers should use the data on hypotension, bandemia, and elevated lactate to increase their clinical suspicion for progression to septic shock, the finding that women were more likely to progress to septic shock requires further interpretation and explanation. The higher rate of progression to septic shock in this study among women conflicts with data from animal models, showing a protective effect of the female sex (2); treatment disparities may be the important contributor. Similar to treatment disparities in other disease states including cardiac catheterization and cardiac arrest therapy, in sepsis, women are less likely to have early goal-directed therapy, are less likely to have central catheters placed, and have longer delays to antibiotics (3–5). In a study recently published by our group, the mean time to antibiotics was 18% longer in women with severe sepsis or septic shock compared with men (5). Reasons for these treatment disparities by gender need to be explored further. Treatment disparities could reflect providers’ subconscious biases, differences in patients’ preferences for aggressive care, or even differences in the clinical presentations of patients with sepsis by gender. For example, because of physiologic sex differences, one could speculate that women may appear less ill in the early hours of sepsis compared with men. If women appear less ill, this may lead to delayed recognition of sepsis, treatment delays, and ultimately worse outcomes. It is also unknown whether presenting symptoms of sepsis are the same by gender or whether women have more atypical symptoms. Despite limitations inherent to a retrospective observational study, this study highlights one of the important predictors of progression to septic shock, notably female gender. Further research should investigate potential gender differences in the acute management and clinical presentation of sepsis as potential contributors to this finding. This is critical to help refine our management of patients with sepsis and to eliminate gender disparities in outcomes. The authors have disclosed that they do not have any potential conflicts of interest.
Application of automated feedback for the improvement of data quality in web-based clinical collaborations

Background: Clinical research registries are rarely driven by data quality assurance. However, quality of data can have a huge impact on the performance and outcome of any given trial using registry data. Therefore, data quality assurance procedures for cost reduction and data process improvements have to be implemented in research registries. Hypothesis: This research proposes that web-based data quality feedback can motivate registry users, increase their contributions and ultimately improve the quality of registry data and its (re-)use to support clinical trials; thereby reducing the costs and need for study monitors. Method: To explore causes of low data quality and user motivation, a survey and an assessment of quality indicators in a multicentre clinical setting was performed. Subsequently, a development and evaluation of a web-based feedback framework was conducted. This was explored in the international Niemann-Pick disease registry (INPDR) and two clinical trials associated with the European Network for the Study of Adrenal Tumours (ENSAT). Results: The survey and framework evaluation highlight effectiveness of web-based automated data quality feedback. Case studies showed an increase of data quality within observation time. Conclusion: Centralised data monitoring requires a general framework that can be adjusted for a variety of trials and studies. This research highlights how biomedical research registries have to be designed with focus on data quality and feedback mechanisms.
Generalized Moment Analysis of Magnetic Field Correlations for Accumulations of Spherical and Cylindrical Magnetic Perturbers

In biological tissue, an accumulation of similarly shaped objects with a susceptibility difference to the surrounding tissue generates a local distortion of the external magnetic field in magnetic resonance imaging. It induces stochastic field fluctuations that characteristically influence proton spin diffusion in the vicinity of these magnetic perturbers. The magnetic field correlation that is associated with such local magnetic field inhomogeneities can be expressed in the form of a dynamic frequency autocorrelation function that is related to the time evolution of the measured magnetization. Here, an eigenfunction expansion for two simple magnetic perturber shapes, that of spheres and cylinders, is considered for restricted spin diffusion in a simple model geometry. Then, the concept of generalized moment analysis, an approximation technique that is applied in the study of (non-)reactive processes that involve Brownian motion, allows to provide analytical expressions for the correlation function for different exponential decay forms. Results for the biexponential decay for both spherical and cylindrical magnetized objects are derived and compared with the frequently used (less accurate) monoexponential decay forms. They are in asymptotic agreement with the numerically exact value of the correlation function for long and short times.
The Glycoprotein VI-Phospholipase C&ggr;2 Signaling Pathway Controls Thrombus Formation Induced by Collagen and Tissue Factor In Vitro and In Vivo

Objective—Both collagen and tissue factor can be initiating factors in thrombus formation. We investigated the signaling pathway of collagen-induced platelet activation in interaction with tissue factor–triggered coagulation during the thrombus-forming process. Methods and Results—In murine blood flowing over collagen, platelet exposure of phosphatidylserine and procoagulant activity, but not adhesion, completely relied on each of the following signaling modules: glycoprotein VI (GPVI), FcR &ggr;-chain, Src kinases, adaptor protein LAT, and phospholipase C&ggr;2 (PLC&ggr;2). On flow in the presence of tissue factor, these signaling components were essential for platelet aggregation and greatly enhanced fibrin clot formation. Collagen-stimulated thrombin generation relied on the presence and activity of GPVI, FcR &ggr;-chain, Src kinase, LAT, and PLC&ggr;2. The physiological importance of this GPVI pathway was shown in a FeCl3-induced in vivo murine thrombosis model. In both venules and arterioles, signaling through GPVI, FcR &ggr;-chain, and Src kinases enhanced the formation of phosphatidylserine-exposing and fibrin-rich thrombi. Conclusions—The GPVI-PLC&ggr;2 activation pathway regulates collagen-dependent coagulation in venous and arterial thrombus formation.
Decreased Self-Concept Clarity in People with Schizophrenia

Abstract Disturbances in the perception of self are thought to be central to the development of psychosis. Self-concept clarity (SCC) is the extent to which one’s beliefs about oneself are internally consistent, stable, and clear. Participants with schizophrenia (N = 54) and healthy controls (N = 32) completed the Me Not-Me Decision Task (MNMDT), in which they decided whether 60 adjectives (30 pairs of antonyms) did or did not describe themselves. SCC is conceptualized as the number of consistent responses. Participants also completed the Self-Concept Clarity Scale (SCCS). Compared to healthy controls, participants with schizophrenia scored lower on the MNMDT and SCCS, and scores were negatively correlated with positive and negative symptoms. In a simultaneous regression, SCCS scores were uniquely associated with positive symptoms, whereas MNMDT scores were uniquely associated with negative symptoms. This suggests that people with schizophrenia have decreased self-concept clarity that is related to positive and negative symptoms.
Intradermal injection of an anti‐Langerin‐HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo

The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine‐targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti‐Langerin‐HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti‐HIV immune response without requirement of an adjuvant. Although the co‐injection of the TLR‐7/8 synthetic ligand, R‐848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA‐DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine‐targeted epidermal LCs and R‐848.
Model for MLL translocations in therapy-related leukemia involving topoisomerase IIβ-mediated DNA strand breaks and gene proximity

Topoisomerase poisons such as the epipodophyllotoxin etoposide are widely used effective cytotoxic anticancer agents. However, they are associated with the development of therapy-related acute myeloid leukemias (t-AMLs), which display characteristic balanced chromosome translocations, most often involving the mixed lineage leukemia (MLL) locus at 11q23. MLL translocation breakpoints in t-AMLs cluster in a DNase I hypersensitive region, which possesses cryptic promoter activity, implicating transcription as well as topoisomerase II activity in the translocation mechanism. We find that 2–3% of MLL alleles undergoing transcription do so in close proximity to one of its recurrent translocation partner genes, AF9 or AF4, consistent with their sharing transcription factories. We show that most etoposide-induced chromosome breaks in the MLL locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIβ, but that topoisomerase IIα and -β occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of MLL translocation breakpoints in t-AML. We propose a model where DNA double-strand breaks (DSBs) introduced by topoisomerase IIβ into pairs of genes undergoing transcription within a common transcription factory become stabilized by antitopoisomerase II drugs such as etoposide, providing the opportunity for illegitimate end joining and translocation.
The Spatial Profile of Macular Pigments Is Related to the Topological Characteristics of the Foveal Avascular Zone.

PURPOSE Macular pigments are preferentially concentrated in the central fovea, an area devoid of vasculature. We hypothesized that there may be a link between the macular pigment profile and the size and structural characteristics of the foveal avascular zone (FAZ). METHODS Two-wavelength autofluorescence method was used to quantify macular pigment optical density (MPOD) and the radius at half peak of MPOD, which was defined as the retinal eccentricity where the MPOD value was 50% of the peak value. Volumetric spectral-domain optical coherence tomography (OCT) images of the macula were obtained from 32 subjects. The equivalent radius of the FAZ was determined using data generated from OCT angiography. Generalized estimating equations were used to test the hypothesis that there are interrelationships among the central foveal thickness, peak MPOD, the radius at half peak of MPOD and the equivalent radius of the FAZ. RESULTS The equivalent radius of the FAZ was highly correlated with the radius at half peak of MPOD (P < .001). The equivalent radius of the FAZ was a significant predictor for central foveal thickness (P < .001). The significant predictor for peak MPOD was central foveal thickness (P = .004). Eyes with larger FAZs were more likely to have a secondary peak in their MPOD spatial profile in a zone ranging from 0.5 to 1.0 degrees from the foveal center. CONCLUSIONS The spatial distribution of macular pigment is related to the size of the FAZ, in addition to the central foveal thickness. It is possible that xanthophyll pigment accumulation in the macula serves functions, such as attenuation of shorter wavelengths of light, that would have been provided by the light-filtering characteristics of blood vessels.
Better to be equal? Challenges to equality for cognitively able children with autism spectrum disorders in a social decision game

Much controversy surrounds questions about whether humans have an aversion to inequity and how a commitment to equality might play a role in cooperation and other aspects of social interactions. Examining the social decisions of children with autism spectrum disorders provides a fascinating opportunity to explore these issues. Specifically, we evaluated the possibility that children with autism spectrum disorders may be less likely than typically developing children to show a prioritisation of equality. A total of 69 typically developing (mean age 11;6 years) and 57 cognitively able children with autism spectrum disorders (mean age 11;7 years) played a social decision game in which the equality option was pitted against alternatives that varied in instrumental outcomes. Results showed that both groups were more likely to choose the equality option when there was no cost to the self. However, even though children with autism spectrum disorders appeared to view equality as preferable to causing explicit harm to others, they departed from an equality stance when there was an opportunity to increase instrumental gain without any obvious harm to the self or the other. Typically developing children, in contrast, showed similar prioritisation of equality across these contexts. Future research needs to address the question of how differences in the commitment to equality affect children’s social behaviour and relationships in daily life.
The Molecular Toxicology of Acetaminophen

The history of the development of the analgestic drug acetaminophen is reviewed with an emphasis on the characteristics of its overdose toxicity. The P450-catalyzed oxidation of acetaminophen generates a reactive electrophile that binds covalently to proteins. Involvement of specific P450 enzymes in acetaminophen toxicity can be probed by experiments with knock-out mice. The identification of specific target proteins may help to clarify the mechanism of acetaminophen hepatoxocity.
Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis

Pancreatic ductal carcinoma is one of the malignant diseases with the poorest prognosis. To develop effective methods for better treatment of pancreatic cancer patients, we tried to analyze the course of multistep carcinogenesis of the pancreatic ductal cells. IPMT (intraductal papillary‐mucinous tumor) is thought to be one of the premalignant lesions of the pancreas, which would transform into carcinomas. Loss of 18q at the SMAD4 locus is known to be an early genetic change in pancreatic ductal carcinomas. It is not clear, however, whether or not the target gene for inactivation is SMAD4. Using 18 IPMTs, we analyzed LOH at the SMAD4 locus and observed frequent LOH (7/14, 50%). No mutations were observed in any of the tumors. Moreover, the expression level of the SMAD4 protein did not show a reduction in IPMTs. These results suggested that (i) inactivating mutation of the SMAD4 gene is a rather late genetic change in pancreatic carcinogenesis, and (ii) there may be an unknown tumor suppressor gene in 18q, other than SMAD4, that is involved in pancreatic ductal carcinogenesis. © 2001 Wiley‐Liss, Inc.
Sleep and Epilepsy are Bedfellows

Recent sleep research provides us new data solving several hidden aspects of epilepsies. Intent of this short note is to call attention to the newly revealed interrelationships of epilepsy and NREM sleep. The main underlying engine behind activation of epilepsy in sleep is that NREM sleep put into motion the burst-firing mode of the cortico-thalamic system and develops extended and extremely synchronized slow oscillation and spindling over wide fields of the cortex offering large scope for epileptic synchronization. Sleep research revealed that the same slow wave and spindle activity which gates interictal and ictal epileptic manifestations is the substrate of sleep homeostasis and is responsible for renewing the daily potenciated synapses to make them again possible to learn. Epilepsy is a derailment of plasticity; enlarging synchronised neuronal excitation in neoand archi-cortical plasticity prone brain structures interfering with sleep plasticity functions. Therefore the marriage of sleep and epilepsy is a deadly clasp; a vitious circle like cascade develops: NREM sleep slow wave and spindling gates epilepsy and the epileptic activation interferes with sleep plastic functions may cause chronic enduring cognitive impairment. This kind of pathomechanism is detected with different degree of severity in several epileptic syndromes constituting around more than half of the epileptic population. In the clinical practice only dignostic sleep studies are able to detect this insidious process in our patients.
The Neutral Endopeptidase Inhibitor, SCH 34826, Reduces Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

Summary: SCH 34826, i.e., (S)-N-(N-{2,2[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-2-oxo-1-(phenyl-methyl)ethyl}-L-phenylalanyl)-β-alanine, is a potent and selective inhibitor of neutral endopeptidase 24.11 (NEP), an enzyme that degrades the atrial natriuretic peptide (ANP). The effects of SCH 34826 on hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) were evaluated following 1 month of treatment by measuring the blood pressure, cardiac weight, and left ventricular fibrosis. Adult SHRs were treated with SCH 34826 at 10, 30, or 100 mg/kg given orally twice daily or with vehicle. The systolic blood pressure (SBP) and heart rate (HR) were recorded weekly by the tail-cuff method. Cardiac structural damage was determined by morphometric analysis. Over the dose range examined, the drug produced no significant changes in either blood pressure or heart rate. Despite the lack of antihypertensive activity, SCH 34826 at 100 mg/kg reduced both the cardiac mass (-10%) and the amount of fibrotic tissue present in the left ventricle (-42%). These data indicate that chronic inhibition of NEP by SCH 34826 interacts with mechanisms underlying myocardial hypertrophy and cardiac remodeling.
Analyzing Semantic Change in Japanese Loanwords

We analyze semantic changes in loanwords from English that are used in Japanese (Japanese loanwords). Specifically, we create word embeddings of English and Japanese and map the Japanese embeddings into the English space so that we can calculate the similarity of each Japanese word and each English word. We then attempt to find loanwords that are semantically different from their original, see if known meaning changes are correctly captured, and show the possibility of using our methodology in language education.
Dendritic Co‐stratification of ON and ON‐OFF directionally selective ganglion cells with starburst amacrine cells in rabbit retina

The morphology, dendritic branching patterns, and dendritic stratification of retinal ganglion cells have been studied in Golgi‐impregnated, whole‐mount preparations of rabbit retina. Among a large number of morphological types identified, two have been found that correspond to the morphology of ON and ON‐OFF directionally selective (DS) ganglion cells identified in other studies. These cells have been characterized in the preceeding paper in terms of their cell body size, dendritic field size, and branching pattern. In this paper, the two kinds of DS ganglion cell are compared in terms of their levels of dendritic stratification. They are compared with each other and also with examples of class III.1 cells, defined in the preceding paper with reference to our previous studies.