Miracle-dz/UniFAR-FTUs huggingface dataset:
In Rheumatoid Arthritis, Synovitis at Different Inflammatory Sites Is Dominated by Shared but Patient-Specific T Cell Clones

Genetic and immunological evidence clearly points to a role for T cells in the pathogenesis of rheumatoid arthritis (RA). Selective targeting of such disease-associated T cell clones might be highly effective while having few side effects. However, such selective targeting may only be feasible if the same T cell clones dominate the immune response at different sites of inflammation. We leveraged high-throughput technology to quantitatively assess whether different T cell clones dominate the inflammatory infiltrate at various sites of inflammation in this prototypic autoimmune disease. In 13 RA patients, we performed quantitative next-generation sequencing–based human TCRβ repertoire analysis in simultaneously obtained samples from inflamed synovial tissue (ST) from distinct locations within one joint, from multiple joints, and from synovial fluid (SF) and peripheral blood (PB). Identical TCRβ clones dominate inflammatory responses in ST samples taken from different locations within a single joint and when sampled in different joints. Although overall ST–SF overlap was comparable to higher ST–ST values, the overlap in dominant TCRβ clones in ST–SF comparisons was much lower than ST–ST and comparable to the low ST–PB overlap. In individual RA patients, a limited number of TCRβ clones dominate the immune response in the inflamed ST regardless of the location within a joint and which joint undergoes biopsy; in contrast, there is limited overlap of ST with SF or PB TCR repertoires. This limited breadth of the T cell response in ST of the individual RA patient indicates that development of immunotherapies that selectively modulate dominant T cell responses might be feasible.
Direct Observation of Hydrangea Blue-Complex Composed of 3-O-Glucosyldelphinidin, Al3+ and 5-O-Acylquinic Acid by ESI-Mass Spectrometry

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely anthocyanin, Al3+ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in an aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have not been successful to date. Instead, via experiments mixing 1, Al3+ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al3+ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al3+ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al3+ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al3+ and 2 or 3.
Oxidative Stress in Patients with Drug Resistant Partial Complex Seizure

Oxidative stress (OS) has been implicated as a pathophysiological mechanism of drug-resistant epilepsy, but little is known about the relationship between OS markers and clinical parameters, such as the number of drugs, age onset of seizure and frequency of seizures per month. The current study’s aim was to evaluate several oxidative stress markers and antioxidants in 18 drug-resistant partial complex seizure (DRPCS) patients compared to a control group (age and sex matched), and the results were related to clinical variables. We examined malondialdehyde (MDA), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), nitric oxide (NO), uric acid, superoxide dismutase (SOD), glutathione, vitamin C, 4-hydroxy-2-nonenal (4-HNE) and nitrotyrosine (3-NT). All markers except 4-HNE and 3-NT were studied by spectrophotometry. The expressions of 4-HNE and 3-NT were evaluated by Western blot analysis. MDA levels in patients were significantly increased (p ≤ 0.0001) while AOPP levels were similar to the control group. AGEs, NO and uric acid concentrations were significantly decreased (p ≤ 0.004, p ≤ 0.005, p ≤ 0.0001, respectively). Expressions of 3-NT and 4-HNE were increased (p ≤ 0.005) similarly to SOD activity (p = 0.0001), whereas vitamin C was considerably diminished (p = 0.0001). Glutathione levels were similar to the control group. There was a positive correlation between NO and MDA with the number of drugs. The expression of 3-NT was positively related with the frequency of seizures per month. There was a negative relationship between MDA and age at onset of seizures, as well as vitamin C with seizure frequency/month. We detected an imbalance in the redox state in patients with DRCPS, supporting oxidative stress as a relevant mechanism in this pathology. Thus, it is apparent that some oxidant and antioxidant parameters are closely linked with clinical variables.
Design optimization of the graded AlGaN/GaN HEMT device performance based on material and physical dimensions

Purpose To design and optimize the traditional aluminum gallium nitride/gallium nitride high electron mobility transistor (HEMT) device in achieving improved performance and current handling capability using the Synopsys’ Sentaurus TCAD tool. Design/methodology/approach Varying material and physical considerations, specifically investigating the effects of graded barriers, spacer interlayer, material selection for the channel, as well as study of the effects in the physical dimensions of the HEMT, have been extensively carried out. Findings Critical figure-of-merits, specifically the DC characteristics, 2DEG concentrations and mobility of the heterostructure device, have been evaluated. Significant observations include enhancement of maximum current density by 63 per cent, whereas the electron concentration was found to propagate by 1,020 cm−3 in the channel. Practical implications This work aims to provide tactical optimization to traditional heterostructure field effect transistors, rendering its application as power amplifiers, Monolithic Microwave Integrated Circuit (MMICs) and Radar, which requires low noise performance and very high radio frequency design operations. Originality/value Analysis in covering the breadth and complexity of heterostructure devices has been carefully executed through extensive TCAD modeling, and the end structure obtained has been optimized to provide best performance.
Target of rapamycin complex 2–dependent phosphorylation of the coat protein Pan1 by Akl1 controls endocytosis dynamics in Saccharomyces cerevisiae

Target of rapamycin complex 2 (TORC2) is a widely conserved serine/threonine protein kinase. In the yeast Saccharomyces cerevisiae, TORC2 is essential, playing a key role in plasma membrane homeostasis. In this role, TORC2 regulates diverse processes, including sphingolipid synthesis, glycerol production and efflux, polarization of the actin cytoskeleton, and endocytosis. The major direct substrate of TORC2 is the AGC-family kinase Ypk1. Ypk1 connects TORC2 signaling to actin polarization and to endocytosis via the flippase kinases Fpk1 and Fpk2. Here, we report that Fpk1 mediates TORC2 signaling to control actin polarization, but not endocytosis, via aminophospholipid flippases. To search for specific targets of these flippase kinases, we exploited the fact that Fpk1 prefers to phosphorylate Ser residues within the sequence RXS(L/Y)(D/E), which is present ∼90 times in the yeast proteome. We observed that 25 of these sequences are phosphorylated by Fpk1 in vitro. We focused on one sequence hit, the Ark/Prk-family kinase Akl1, as this kinase previously has been implicated in endocytosis. Using a potent ATP-competitive small molecule, CMB4563, to preferentially inhibit TORC2, we found that Fpk1-mediated Akl1 phosphorylation inhibits Akl1 activity, which, in turn, reduces phosphorylation of Pan1 and of other endocytic coat proteins and ultimately contributes to a slowing of endocytosis kinetics. These results indicate that the regulation of actin polarization and endocytosis downstream of TORC2 is signaled through separate pathways that bifurcate at the level of the flippase kinases.
Comparison of three eye tracking devices in psychology of programming research

Eye tracking can be used in measuring point of gaze data that provides information concerning subject’s focus of attention. The focus of subject’s attention can be used as supportive evidence in studying cognitive processes. Despite the potential usefulness of eye tracking in psychology of programming research, there exists only few instances where eye tracking has actually been used. This paper presents an experiment in which we used three eye tracking devices to record subjects’ points of gaze when they were studying short computer programs using a program animator. The results suggest that eye tracking can be used to collect relatively accurate data for the purposes of psychology of programming research. The results also revealed significant differences between the devices in the accuracy of the point of gaze data and in the times needed for setting up the monitoring process.
THE OCCURRENCE AND PERCEPTION OF LISTENER VISUAL CUES DURING NONUNDERSTANDING EPISODES

Abstract This research report examines the occurrence of listener visual cues during nonunderstanding episodes and investigates raters’ sensitivity to those cues. Nonunderstanding episodes (n = 21) and length-matched understanding episodes (n = 21) were taken from a larger dataset of video-recorded conversations between second language (L2) English speakers and a bilingual French-English interlocutor (McDonough, Trofimovich, Dao, & Abashidze, 2018). Episode videos were analyzed for the occurrence of listener visual cues, such as head nods, blinks, facial expressions, and holds. Videos of the listener’s face were manipulated to create three rating conditions: clear voice/clear face, distorted voice/clear face, and clear voice/blurred face. Raters in the same speech community (N = 66) were assigned to a video condition to assess the listener’s comprehension. Results revealed differences in the occurrence of listener visual cues between the understanding and nonunderstanding episodes. In addition, raters gave lower ratings of listener comprehension when they had access to the listener’s visual cues.
LncRNA TNRC6C‐AS1 regulates UNC5B in thyroid cancer to influence cell proliferation, migration, and invasion as a competing endogenous RNA of miR‐129‐5p

To investigate the biological functions and regulatory mechanism of lncRNA TNRC6C‐AS1 in thyroid cancer (TC). TNRC6C‐AS1, miR‐129‐5p, and UNC5B expression levels were investigated by qRT‐PCR and Western blot. CCK‐8 assay was conducted to determine cell proliferation, while transwell assay was for inspection of cell migration and invasion. Through bioinformatic analysis, the interactions among TNRC6C‐AS1, miR‐129‐5p, and UNC5B were predicted. Dual luciferase reporter gene assay and RNA pull‐down assay confirmed the predicted target relationships. Tumor xenograft assay was applied to inspect the effect of TNRC6C‐AS1 downregulation on TC development in vivo. TNRC6C‐AS1 and UNC5B were overexpressed, while miR‐129‐5p was underexpressed in TC tissues and cells. TNRC6C‐AS1/UNC5B downregulation and miR‐129‐5p overexpression could suppress proliferation, migration, and invasion of TC cells as well as inhibit tumorigenesis in vivo. MiR‐129‐5p targeted TNRC6C‐AS1 and UNC5B in TC cells; and UNC5B expression was downregulated by knocking down TNRC6C‐AS1, which competitively bound with miR‐129‐5p. Downregulation of TNRC6C‐AS1 restrained TC development by knocking down UNC5B through upregulating the expression of miR‐129‐5p.
Nurses’ knowledge regarding pain management in high acuity care units: A case study of Palestine

Background: Most patients who have been hospitalized at some point in time must have experienced a measure of pain despite improvements in health-care systems. Globally, there is a dearth in information with regard to pain management. Pain management is an essential process for nurses because they spend most time of the day with the patients. Therefore, nurses’ level of knowledge and positive attitudes toward pain management reflect this vital and significant role played by nurses in critical care units. Aims: The aims of this are to evaluate the level of knowledge and attitude of nurses regarding pain management in high acuity care units of Palestine. Methods: For this cross-sectional descriptive study, data were obtained from seven hospitals in Palestine. Nurses were recruited from high acuity care units, including nurses from the medical and surgical wards. Their knowledge on the degree of pain was measured using the survey for “Knowledge and Attitudes Survey Regarding Pain. ” Results: About 123 nurses took part in the survey. The total mean score of correct answers for the 39 questions asked was 17.4 ± 4.2, which is considered to be less than the pass mark of 19.5. There were no statistically significant differences between the nurses’ total average score and demographic characteristics, except for their initial level of education. Conclusions: The results of this study showed that Palestinian nurses in critical care units possess inadequate knowledge about pain management. Furthermore, there are inconsistencies in their attitudes and practices which require further research. There is a need for the council of health professionals to lay emphasis on pain management through continuous training and enlightenment of nurses to equip them with more knowledge and positive attitudes toward pain management.
Social modulation of fear: Facilitation vs buffering

Social behaviors largely constitute mutual exchanges of social cues and the responses to them. The adaptive response also requires proper interpretation of the current context. In fear behaviors, social signals have bidirectional effects—some cues elicit or enhance fear whereas other suppress or buffer it. Studies on the social facilitation and social buffering of fear provide evidence of competition between social cues of opposing meanings. Co‐expression of opposing cues by the same animal may explain the contradicting outcomes from the interaction between naive and frightened conspecifics, which reflect the fine balance between fear facilitation and buffering. The neuronal mechanisms that determine that balance provide an exciting target for future studies to probe the brain circuits underlying social modulation of emotional behaviors.
Glucose and Prolactin Monitoring in Children and Adolescents Initiating Antipsychotic Therapy

Abstract Objective: We aimed to evaluate glucose and prolactin monitoring in children and adolescents initiating antipsychotic therapy using a nationwide claims database. Methods: A retrospective 15-month cohort study was conducted using the National Database of Health Insurance Claim Information and Specified Medical Checkups in Japan. Patients aged ≤18 years, who were newly prescribed antipsychotics between April 2014 and March 2015, were followed up for 450 days. Outcomes were the use of glucose and prolactin testing through 15 months after drug initiation (index date) with consideration of persistence with antipsychotic therapy. The incidence proportion of patients monitored was assessed within the following four time windows: baseline (between 30 days before the index date and the index date), at 1–3 months (between 1 and 90 days after the index date), at 4–9 months (between 91 and 270 days after the index date), and at 10–15 months (between 271 and 450 days after the index date). Results: Of 43,608 new users in 6620 medical institutions, the percentage of persistent antipsychotic users was 46.4% at 90 days, 29.7% at 270 days, and 23.8% at 450 days after the index date. The proportion of patients who received monitoring within the baseline period was 13.5% (95% confidence interval [CI], 13.2–13.8) for glucose and 0.6% (95% CI, 0.5–0.6) for prolactin, respectively. The proportion of patients who received glucose monitoring at all time windows decreased to 0.9%. The proportion of patients who received prolactin monitoring by the second time window decreased to 0.1%. Conclusions: Our study shows that monitoring for glucose and prolactin is infrequent in children and adolescents initiating antipsychotic therapy. Strategies for physicians, patients, and guardians are needed to overcome the barriers in glucose and prolactin monitoring.
False Alarms and Overmonitoring

Supplemental Digital Content is Available in the Text. Background: Nurses can be exposed to hundreds of alarms during their shift, contributing to alarm fatigue. Purpose: The purposes were to explore similarities and differences in perceptions of clinical alarms by labor nurses caring for generally healthy women compared with perceptions of adult intensive care unit (ICU) and neonatal ICU nurses caring for critically ill patients and to seek nurses' suggestions for potential improvements. Methods: Nurses were asked via focus groups about the utility of clinical alarms from medical devices. Results: There was consensus that false alarms and too many devices generating alarms contributed to alarm fatigue, and most alarms lacked clinical relevance. Nurses identified certain types of alarms that they responded to immediately, but the vast majority of the alarms did not contribute to their clinical assessment or planned nursing care. Conclusions: Monitoring only those patients who need it and only those physiologic values that are warranted, based on patient condition, may decrease alarm burden.
Downregulation of p‐COUMAROYL ESTER 3‐HYDROXYLASE in rice leads to altered cell wall structures and improves biomass saccharification

p-Coumaroyl ester 3-hydroxylase (C3'H) is a key enzyme involved in the biosynthesis of lignin, a phenylpropanoid polymer that is the major constituent of secondary cell walls in vascular plants. Although the crucial role of C3'H in lignification and its manipulation to upgrade lignocellulose have been investigated in eudicots, limited information is available in monocotyledonous grass species, despite their potential as biomass feedstocks. Here we address the pronounced impacts of C3'H deficiency on the structure and properties of grass cell walls. C3'H-knockdown lines generated via RNA interference (RNAi)-mediated gene silencing, with about 0.5% of the residual expression levels, reached maturity and set seeds. In contrast, C3'H-knockout rice mutants generated via CRISPR/Cas9-mediated mutagenesis were severely dwarfed and sterile. Cell wall analysis of the mature C3'H-knockdown RNAi lines revealed that their lignins were largely enriched in p-hydroxyphenyl (H) units while being substantially reduced in the normally dominant guaiacyl (G) and syringyl (S) units. Interestingly, however, the enrichment of H units was limited to within the non-acylated lignin units, with grass-specific γ-p-coumaroylated lignin units remaining apparently unchanged. Suppression of C3'H also resulted in relative augmentation in tricin residues in lignin as well as a substantial reduction in wall cross-linking ferulates. Collectively, our data demonstrate that C3'H expression is an important determinant not only of lignin content and composition but also of the degree of cell wall cross-linking. We also demonstrated that C3'H-suppressed rice displays enhanced biomass saccharification.
Otopathologic Changes in the Cochlea following Head Injury without Temporal Bone Fracture

Objective Hearing loss following temporal bone (TB) fracture may result from direct transection of the middle and inner ear. The pathophysiology of hearing loss due to head injury without TB fracture, however, is not well understood. Few reports describe otopathologic findings. Herein, we investigate the pathologic findings of patients who sustained a head injury without evidence of a TB fracture. Study Design Otopathology study. Setting Otopathology laboratory. Subjects Subjects with a history of head injury without TB fracture. Methods The TBs of patients with head injury were evaluated by light microscopy. Inner ear anatomy was evaluated, including counts of spiral ganglion cells (SGCs), hair cells, pillar cells, atrophy of the stria vascularis, and the presence of endolymphatic hydrops. SGC counts were compared with those of historical age-matched controls. Results All cases (N = 6 TBs) had evidence of inner ear pathology. Of the 6 cases, 2 (33%) had severe loss of hair cells in all 3 turns of the cochlea, and 4 (67%) cases demonstrated moderate to severe loss at the basal turn of the cochlea. Four cases had scattered atrophy of the stria vascularis, and 3 (50%) had cochlear hydrops. The number of total SGCs was decreased, with an average 53% loss (range, 25%-79%) as compared with controls. The SGC count loss was evenly distributed along Rosenthal’s canal. Conclusions Patients with a history of head injury without TB fracture demonstrate inner ear pathology. Further studies are necessary to determine if otopathology findings are directly attributable to trauma.
RF coils: A practical guide for nonphysicists

Radiofrequency (RF) coils are an essential MRI hardware component. They directly impact the spatial and temporal resolution, sensitivity, and uniformity in MRI. Advances in RF hardware have resulted in a variety of designs optimized for specific clinical applications. RF coils are the “antennas” of the MRI system and have two functions: first, to excite the magnetization by broadcasting the RF power (Tx‐Coil) and second to receive the signal from the excited spins (Rx‐Coil). Transmit RF Coils emit magnetic field pulses ( B1+ ) to rotate the net magnetization away from its alignment with the main magnetic field (B0), resulting in a transverse precessing magnetization. Due to the precession around the static main magnetic field, the magnetic flux in the receive RF Coil ( B1− ) changes, which generates a current I. This signal is “picked‐up” by an antenna and preamplified, usually mixed down to a lower frequency, digitized, and processed by a computer to finally reconstruct an image or a spectrum. Transmit and receive functionality can be combined in one RF Coil (Tx/Rx Coils). This review looks at the fundamental principles of an MRI RF coil from the perspective of clinicians and MR technicians and summarizes the current advances and developments in technology.