Miracle-dz/UniFAR-FTUs huggingface dataset:
Occupant kinematics of the Hybrid III, THOR-M, and postmortem human surrogates under various restraint conditions in full-scale frontal sled tests

ABSTRACT Objective: The objective of this research was to compare the occupant kinematics of the Hybrid III (HIII), THOR-M, and postmortem human surrogates (PMHS) during full-scale frontal sled tests under 3 safety restraint conditions: knee bolster (KB), knee bolster and steering wheel airbag (KB/SWAB), and knee bolster airbag and steering wheel airbag (KBAB/SWAB). Methods: A total of 20 frontal sled tests were performed with at least 2 tests performed per restraint condition per surrogate. The tests were designed to match the 2012 Toyota Camry New Car Assessment Program (NCAP) full-scale crash test. Rigid polyurethane foam surrogates with compressive strength ratings of 65 and 19 psi were used to simulate the KB and KBAB, respectively. The excursions of the head, shoulders, hips, knees, and ankles were collected using motion capture. Linear acceleration and angular velocity data were also collected from the head, thorax, and pelvis of each surrogate. Time histories were compared between surrogates and restraint conditions using ISO/TS 18571. Results: All surrogates showed some degree of sensitivity to changes in restraint condition. For example, the use of a KBAB decreased the pelvis accelerations and the forward excursions of the knees and hips for all surrogates. However, these trends were not observed for the thorax, shoulders, and head, which showed more sensitivity to the presence of a SWAB. The average scores computed using ISO/TS 18571 for the HIII/PMHS and THOR-M/PMHS comparisons were 0.527 and 0.518, respectively. The HIII had slightly higher scores than the THOR-M for the excursions (HIII average = 0.574; THOR average = 0.520). However, the THOR-M had slightly higher scores for the accelerations and angular rates (HIII average = 0.471; THOR average = 0.516). Conclusions: The data from the current study showed that both KBABs and SWABs affected the kinematics of all surrogates during frontal sled tests. The results of the objective rating analysis indicated that the HIII and THOR-M had comparable overall biofidelity scores. The THOR-M slightly outperformed the HIII for the acceleration and angular velocity data. However, the HIII scored slightly better than the THOR-M for the excursion data. The most notable difference in biofidelity was for the knee excursions, where the HIII had a much higher average ISO score. Only the biofidelity of the HIII and THOR-M with regard to occupant kinematics was evaluated in this study; therefore, future work will evaluate the biofidelity of the ATDs in terms of lower extremity loading, thoracic response, and neck loading.
Allergies, antibiotics use, and multiple sclerosis

Abstract Background: The associations between allergies, antibiotics use, and multiple sclerosis (MS) remain controversial and their mediating or moderating effects have not yet been examined. We aimed to assess the direct and indirect influences of allergies and antibiotics use on MS development, and their interactions. Methods: A 1:3 matched case–control study was performed using the National Ambulatory Medical Care Survey database from 2006 to 2013 in the USA. Multiple sclerosis was identified based on the ICD-9 code (340.0) in any position. Cases were matched to their controls based on survey year, age, gender, race, payer type, region, and tobacco use. Allergy diseases and antibiotics prescriptions were extracted by ICD-9 code and drug classification code, respectively. Both generalized structural equation model and MacArthur approach were used to examine their intrinsic relationships. Results: The weighted prevalence of MS was 133.7 per 100,000 visits. A total of 829 MS patients and 2441 controls were matched. Both respiratory tract allergies (OR = 0.29, 95% CI: 0.18, 0.49) and other allergies (OR = 0.38, 95% CI: 0.19, 0.77) were associated with a reduction of the risk of MS. Patients with respiratory tract allergies were more likely to use penicillin (OR = 8.73, 95% CI: 4.12, 18.53) and other antibiotics (OR = 3.77, 95% CI: 2.72, 5.21), and those with other allergies had a higher likelihood of penicillin use (OR = 4.15, 95% CI: 1.27, 13.54); however, the link between antibiotics use and MS was not confirmed although penicillin use might mediate the relationship between allergies and MS. Conclusions: The findings supported allergy as a protective factor for MS development. We also suggest antibiotics use might not be a suitable indicator of bacterial infection to investigate the cause of MS.
Echocardiographic changes after myocardial infarction in a model of left ventricular diastolic dysfunction.

To determine the early and late effects of myocardial infarction on left ventricular (LV) diastolic function in the rabbit postinfarction model, male New Zealand White rabbits were randomly assigned to ligation of the circumflex artery or sham operation. Serial echocardiographic and Doppler studies were performed on both groups of animals at baseline and 1 h and 3 wk after surgery ( n = 10 for each group) after verification of the reproducibility and repeatability of the measurements. At 1 h postinfarction, decreases in early mitral inflow velocity (E wave) and mitral inflow velocity with atrial contraction (A wave) and increases in the mean pulmonary venous systolic-to-diastolic ratio and A wave reversal velocities were observed, without changes in LV geometry. By 3 wk postinfarction, increases in the mitral E-to-A ratio (1.1 ± 0.3 vs. 2.9 ± 0.9, P < 0.001) and left atrial area (131 ± 23 vs. 510 ± 72 mm2, P < 0.001) and decreases in the pulmonary venous systolic-to-diastolic ratio (0.56 ± 0.20 vs. 0.79 ± 0.14, P = 0.008) were consistent with severe diastolic abnormalities (restricted physiology). The findings of this study demonstrate that coronary artery ligation in the rabbit provides a reproducible echocardiographic and Doppler model of LV diastolic dysfunction that is consistent with abnormalities found in humans with previous myocardial infarction, symptoms of heart failure, and preserved LV systolic function.
Simultaneous Excitation of Multiple-Input Multiple-Output CFD-Based Unsteady Aerodynamic Systems

A significant improvement to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) is presented. This improvement involves the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system that enables the computation of the unsteady aerodynamic state-space model using a single CFD execution, independent of the number of structural modes. Four different types of inputs are presented that can be used for the simultaneous excitation of the structural modes. Results are presented for a flexible, supersonic semi-span configuration using the CFL3Dv6.4 code.
Moderate anemia at diagnosis is an independent prognostic marker of the EUTOS, Sokal, and Hasford scores for survival and treatment response in chronic-phase, chronic myeloid leukemia patients with frontline imatinib

Abstract Objectives: This study aimed to examine the prognostic value of anemia for the diagnosis of chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib. Methods: One hundred and fifty-four CML-CP patients were enrolled. The influences of moderate anemia with hemoglobin (Hb) < 10 g/dl, four scoring systems, and the early molecular response at 3 months (BCR-ABL ≤10%; 3M-EMR) on the achievement of a deep molecular response (DMR, MR4.5), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were compared. Results: Moderate anemia was identified in 44 (28.6%) patients. These patients had more aggressive baseline features and higher risks, as assessed by scoring systems, and less favorable treatment responses vs those without anemia, including 3M-EMR (50.0% vs 69.1%), a complete cytogenetic response at 6 months (20.5% vs 50.9%), and a major molecular response at 12 months (22.5% vs 45.2%), with a median follow-up of 54.0 months. Furthermore, an Hb of 10 g/dl better distinguished DMR, EFS, PFS, and OS than the EUTOS, Sokal, and Hasford scores, and better predicted the responses and survivals in combination with 3M-EMR than 3M-EMR alone. Conclusions: This finding highlights the significance of anemia in CML-CP, and suggests that patients with anemia at diagnosis should be carefully monitored and might benefit from more potent TKIs if not achieving 3M-EMR.
Dissecting relative contributions of cis- and trans-determinants to nucleosome distribution by comparing Tetrahymena macronuclear and micronuclear chromatin

The ciliate protozoan Tetrahymena thermophila contains two types of structurally and functionally differentiated nuclei: the transcriptionally active somatic macronucleus (MAC) and the transcriptionally silent germ-line micronucleus (MIC). Here, we demonstrate that MAC features well-positioned nucleosomes downstream of transcription start sites and flanking splice sites. Transcription-associated trans-determinants promote nucleosome positioning in MAC. By contrast, nucleosomes in MIC are dramatically delocalized. Nucleosome occupancy in MAC and MIC are nonetheless highly correlated with each other, as well as with in vitro reconstitution and predictions based upon DNA sequence features, revealing unexpectedly strong contributions from cis-determinants. In particular, well-positioned nucleosomes are often matched with GC content oscillations. As many nucleosomes are coordinately accommodated by both cis- and trans-determinants, we propose that their distribution is shaped by the impact of these nucleosomes on the mutational and transcriptional landscape, and driven by evolutionary selection.
Disciplinary differences of the impact of altmetric

&NA; The main objective of this work was to group altmetric indicators according to their relationships and detect disciplinary differences with regard to altmetric impact in a set of 3793 research articles published in 2013. Three of the most representative altmetric providers (Altmetric, PlumX and Crossref Event Data) and Scopus were used to extract information about these publications and their metrics. Principal component analysis was used to summarize the information on these metrics and detect groups of indicators. The results show that these metrics can be grouped into three components: social media, gathering metrics from social networks and online media; usage, including metrics on downloads and views; and citations and saves, grouping metrics related to research impact and saves in bookmarking sites. With regard to disciplinary differences, articles in the General category attract more attention from social media, Social Sciences articles have higher usage than Physical Sciences, and General articles are more cited and saved than Health Sciences and Social Sciences articles.
Characterization and mechanisms of the pharyngoesophageal inhibitory reflex.

The objectives of this study were to identify and to characterize the pharyngoesophageal inhibitory reflex (PEIR) in an animal model. Thirty-one cats (2.4-5.0 kg) were anesthetized using α-chloralose (45 mg/kg ip), and esophageal peristalsis was recorded manometrically. Secondary peristalsis was activated by rapid air injection (8-20 ml) at midesophagus or slow infusion of water through the manometric catheters. Neither stimulus activated primary peristalsis. The PEIR was activated by rapid water injection or focal mechanical stimulation of the pharynx. Rapid air injection activated secondary peristalsis in 92% of the trials, and slow water infusion activated 1 secondary peristalsis every 3.2 min. Pharyngeal stimulation by 0.3, 0.5, 0.8, or 1.0 ml of water inhibited or blocked ongoing secondary peristalsis in 67, 82, 97, or 93% of trials, respectively. Mechanical stimulation of the posterior wall of the pharynx with 11-20 g pressure attenuated secondary peristalsis in 96% of the trials or blocked secondary peristalsis in 41% of the trials. Centripetal electrical stimulation at 30 Hz, 0.2 ms, 2 V for 4 s of the superior laryngeal (SLN) or glossopharyngeal (GPN) nerves blocked or inhibited secondary peristalsis in 100% of the trials. Bilateral transection of the GPN ( n = 8), but not the SLN ( n = 6), blocked the PEIR. Anesthetization of the pharyngeal mucosa using lidocaine (2%) blocked the PEIR ( n = 3). We concluded that 1) the PEIR exists in the cat, 2) mechanical stimulation of the pharynx more strongly activates the PEIR than water, 3) activation of either SLN or GPN afferents attenuates ongoing secondary peristalsis, 4) the receptors mediating the PEIR are located in the pharyngeal mucosa, and 5) both SLN and GPN contribute to the PEIR, but the GPN is the major afferent limb of this reflex.
Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial

Background: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. Methods: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment. Results: Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups. Conclusions: IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.
Dexamethasone upregulates the Na-K-ATPase in rat alveolar epithelial cells.

Previous studies in kidney, heart, and liver cells have demonstrated that dexamethasone regulates the expression of Na-K-ATPase. In the lungs, Na-K-ATPase has been reported in alveolar epithelial type II (ATII) cells and is thought to participate in active Na+ transport and lung edema clearance. The aim of this study was to determine whether Na-K-ATPase would be regulated by dexamethasone in cultured rat ATII cells. Regulation of the Na-K-ATPase by dexamethasone could lead to a greater understanding of its role in active Na+ transport and lung edema clearance. Rat ATII cells were isolated, plated for 24 h, and exposed to 10-7 and 10-8 M dexamethasone. These cells were harvested at 0, 3, 6, 12, and 24 h after dexamethasone exposure for determination of steady-state Na-K-ATPase mRNA transcript levels, protein expression, and function. The steady-state Na-K-ATPase β1-mRNA transcript levels increased in ATII cells 6, 12, and 24 h after dexamethasone exposure ( P < 0.05). However, the steady-state α1-mRNA transcript levels were unchanged. The protein expression for the α1- and β1-subunits increased in ATII cells exposed to dexamethasone compared with controls in association with a temporal increase in Na-K-ATPase function after dexamethasone exposure. These results suggest that dexamethasone regulates Na-K-ATPase in ATII cells possibly by transcriptional, translational, and posttranslational mechanisms.
Dynamic Alu Methylation during Normal Development, Aging, and Tumorigenesis

DNA methylation primarily occurs on CpG dinucleotides and plays an important role in transcriptional regulations during tissue development and cell differentiation. Over 25% of CpG dinucleotides in the human genome reside within Alu elements, the most abundant human repeats. The methylation of Alu elements is an important mechanism to suppress Alu transcription and subsequent retrotransposition. Decades of studies revealed that Alu methylation is highly dynamic during early development and aging. Recently, many environmental factors were shown to have a great impact on Alu methylation. In addition, aberrant Alu methylation has been documented to be an early event in many tumors and Alu methylation levels have been associated with tumor aggressiveness. The assessment of the Alu methylation has become an important approach for early diagnosis and/or prognosis of cancer. This review focuses on the dynamic Alu methylation during development, aging, and tumor genesis. The cause and consequence of Alu methylation changes will be discussed.
A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis

ABSTRACT Increasing antimicrobial resistance among uropathogens limits treatment options for patients with complicated urinary tract infection (cUTI). Plazomicin, a new aminoglycoside, has in vitro activity against multidrug-resistant Enterobacteriaceae, including isolates resistant to currently available aminoglycosides, as well as extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae. We evaluated the efficacy and safety of plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to receive intravenous plazomicin (10 or 15 mg/kg of body weight) or intravenous levofloxacin (750 mg) once daily for 5 days. Coprimary efficacy endpoints were microbiological eradication at the test of cure (TOC; 5 to 12 days after the last dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME) populations. Overall, 145 patients were randomized to treatment. In the groups receiving plazomicin at 10 mg/kg, plazomicin at 15 mg/kg, and levofloxacin, microbiological eradication rates were, respectively, 50.0% (6 patients with microbiological eradication at TOC/12 patients treated [95% confidence interval {CI}, 21.1 to 78.9%]), 60.8% (31/51 [95% CI, 46.1 to 74.2%]), and 58.6% (17/29 [95% CI, 38.9 to 76.5%]) in the MITT population and 85.7% (6/7 [95% CI, 42.1 to 99.6%]), 88.6% (31/35 [95% CI, 73.3 to 96.8%]), and 81.0% (17/21 [95% CI, 58.1 to 94.6%]) in the ME population. In the MITT population, 66.7% (95% CI, 34.9 to 90.1%), 70.6% (95% CI, 56.2 to 82.5%), and 65.5% (95% CI, 45.7 to 82.1%) of the patients in the three groups, respectively, were assessed by the investigator to be clinically cured at TOC. Adverse events were reported in 31.8%, 35.1%, and 47.7% of the patients in the three groups, respectively. Serum creatinine values were generally stable over the course of the study. No plazomicin-treated patients with evaluable audiometry data had postbaseline sensorineural, conductive, or mixed hearing loss. In summary, plazomicin demonstrated microbiological and clinical success and an overall safety profile supportive of further clinical development. (This study has been registered at ClinicalTrials.gov under identifier NCT01096849.)
A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis

Background: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. Objectives: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. Methods: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. Results: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the –6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. Conclusions: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.
A simplified method for isolation of large numbers of defined nephron segments.

We describe a simplified method for the isolation of large numbers of nephron segments from rat and rabbit kidneys. In contrast to most previous protocols, the kidneys are not perfused. After removal from the animal, the kidney is sliced and torn in pieces that are subsequently digested in culture medium containing 0.5 mg/ml of collagenase at 37°C. If the preparation is agitated only very gently and infrequently, then the tissue gradually falls apart into a suspension containing long nephron fragments, often consisting of multiple connected segments. These are easily sorted into homogeneous segment populations that can be used for enzyme assays, protein extraction for immunoblotting, and RNA extraction for reverse transcription-polymerase chain reaction, all of which have been done successfully in our laboratory. For comparison, we have also examined cortical collecting tubule segments and cells prepared by the more rigorous protocol described previously (E. Schlatter, U. Fröbe, and R. Greger. Pflügers Arch. 421: 381-387, 1992). Even after the isolation of single cells in a Ca2+-free medium, the cells maintain their normal architecture and a distinct separation of apical and basolateral membranes.
A 33 Gb/s combined adaptive CTLE and half-rate look-ahead DFE in 0.13 µm BiCMOS technology for serial link

: A 33 Gbit/s equalizer chip fabricated in 0.13 μm BiCMOS technology is presented. The proposed equalizer prototype includes adaptive continue time linear equalizer (CTLE) with middle frequency compensation and adaptive half-rate look ahead decision feedback equalizer (DFE). The slope detection based CTLE employs a two-path amplifier to adjust the ratio of the high frequency and low frequency adaptively, and a middle frequency amplifier dedicated to provide an appropriate compensation in the intermediate frequency range. For the half-rate DFE, by using a look ahead structure and an analog LMS algorithm circuit, the performance is improved in speed and area. Measurement results show that the equalizer chip can compensate lossy channel with a loss of 26 dB at 20 GHz effectively and the data rate can be up to 33 Gb/s under 3.3 V power supply, the total power consumption is about 726 mW at 33 Gb/s data rate.