Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Ototoxicity Potential of Once-Daily, Single-Entity Hydrocodone in Patients with Chronic Pain: Results of Two Phase-3 Clinical Studies.

BACKGROUND Use/misuse of the opioid combination hydrocodone-acetaminophen has been associated with permanent hearing loss. Although reports have been rare, this potential effect can have significant detrimental effect on patients' overall quality of life. To date, the ototoxic effect of hydrocodone alone has not been systematically investigated. OBJECTIVE In this report, we aimed to evaluate the potential ototoxicity of a novel, single-entity, once-daily, extended-release hydrocodone tablet (Hysingla® ER; HYD). STUDY DESIGN Clinical study. SETTING Audiology clinics in US. METHODS Results from 1207 patients in two phase 3 clinical studies were evaluated: A placebo-controlled study with an enriched enrollment, randomized withdrawal design in patients with chronic low back pain, and an open-label, long-term, safety study in patients with chronic nonmalignant and non-neuropathic pain. Comprehensive audiologic assessments (comprising pure-tone air-conduction audiometry in the conventional [0.25-8 kHz] and ultra-high [10-16 kHz] frequencies, pure-tone bone-conduction audiometry, tympanometry, speech reception thresholds, and word recognition) were conducted at baseline and end-of-studies; air-conduction audiometry was conducted periodically during the studies. All audiologic assessments were performed in audiology clinics in the United States by licensed audiologists. The primary endpoint was changes from baseline in pure-tone air-conduction thresholds in the conventional frequencies during the studies. These trials are registered with ClinicalTrials.gov, identifiers NCT01400139 and NCT01452529. RESULTS During the studies, mean changes from baseline in air-conduction thresholds were clinically unremarkable. Bidirectional variability across all test frequencies was observed; 82% of patients did not experience significant threshold changes during the studies, 7% had potential hearing decrement, and 10% experienced hearing sensitivity improvement. No notable differences were observed between patients receiving HYD and placebo or between different HYD doses. CONCLUSION No ototoxic signal was observed for single-entity hydrocodone tablets at the dosages and treatment durations investigated. Key words: Audiologic monitoring, clinical trials, hydrocodone, opioids, ototoxicity monitoring, sensorineural hearing loss.
STAT2-Dependent Immune Responses Ensure Host Survival despite the Presence of a Potent Viral Antagonist

ABSTRACT A pathogen encounter induces interferons, which signal via Janus kinases and STAT transcription factors to establish an antiviral state. However, the host and pathogens are situated in a continuous arms race which shapes host evolution toward optimized immune responses and the pathogens toward enhanced immune-evasive properties. Mouse cytomegalovirus (MCMV) counteracts interferon responses by pM27-mediated degradation of STAT2, which directly affects the signaling of type I as well as type III interferons. Using MCMV mutants lacking M27 and mice lacking STAT2, we studied the opposing relationship between antiviral activities and viral antagonism in a natural host-pathogen pair in vitro and in vivo. In contrast to wild-type (wt) MCMV, ΔM27 mutant MCMV was efficiently cleared from all organs within a few days in BALB/c, C57BL/6, and 129 mice, highlighting the general importance of STAT2 antagonism for MCMV replication. Despite this effective and relevant STAT2 antagonism, wt and STAT2-deficient mice exhibited fundamentally different susceptibilities to MCMV infections. MCMV replication was increased in all assessed organs (e.g., liver, spleen, lungs, and salivary glands) of STAT2-deficient mice, resulting in mortality during the first week after infection. Taken together, the results of our study reveal the importance of cytomegaloviral interferon antagonism for viral replication as well as a pivotal role of the remaining STAT2 activity for host survival. This mutual influence establishes a stable evolutionary standoff situation with fatal consequences when the equilibrium is disturbed. IMPORTANCE The host limits viral replication by the use of interferons (IFNs), which signal via STAT proteins. Several viruses evolved antagonists targeting STATs to antagonize IFNs (e.g., cytomegaloviruses, Zika virus, dengue virus, and several paramyxoviruses). We analyzed infections caused by MCMV expressing or lacking the STAT2 antagonist pM27 in STAT2-deficient and control mice to evaluate its importance for the host and the virus in vitro and in vivo. The inability to counteract STAT2 directly translates into exaggerated IFN susceptibility in vitro and pronounced attenuation in vivo. Thus, the antiviral activity mediated by IFNs via STAT2-dependent signaling drove the development of a potent MCMV-encoded STAT2 antagonist which became indispensable for efficient virus replication and spread to organs required for dissemination. Despite this clear impact of viral STAT2 antagonism, the host critically required the remaining STAT2 activity to prevent overt disease and mortality upon MCMV infection. Our findings highlight a remarkably delicate balance between host and virus.
Lebensentwürfe, Lebensformen und Lebensqualität

Zusammenfassung Die deutsche Vereinigung hat zwei Gesellschaften mit unterschiedlichen Erwerbsmustern (speziell von Frauen), unterschiedlichen Rollen- und Familienbildern und einer unterschiedlichen Struktur von Haushaltsund Familienformen zusammengeführt. Dies führt zu der Frage, ob sich diese Unterschiede im gesamtdeutschen Transformationsprozeß fortsetzen oder ob eine Angleichung stattfindet. In diesem Beitrag wird auf der Grundlage von Daten des Sozio-ökonomischen Panels die jüngste Entwicklung der Haushalts- und Familienformen in Ost und West nachgezeichnet und ihre jeweiligen Wohlfahrtspositionen anhand zentraler Indikatoren ermittelt und verglichen. Zentrales Ergebnis ist, daß noch immer erhebliche Unterschiede in den Haushalts- und Erwerbskonstellationen bestehen: In Ostdeutschland ist trotz einer zunehmenden Pluralität das Vollzeit erwerbstätige Paar mit Kind(ern) unter 16 Jahren die häufigste Lebensform, während sie in Westdeutschland unter den zehn häufigsten Haushalts- und Erwerbskonstellationen nicht vertreten ist. Die einzelnen Lebensformen weisen in Ost und West trotz unterschiedlicher Verbreitung hinsichtlich der Wohlfahrtspositionen überraschende Ähnlichkeiten auf. In bezug auf die unterschiedlichen Rollen- und Familienbilder kann von einer Angleichung nicht die Rede sein. So gibt es bislang keine Anzeichen dafür, daß sich die ostdeutschen Frauen mit dem westdeutschen Familien- und Erwerbsmodell arrangieren.
Functional liver tissue engineering by an adult mouse liver‐derived neuro‐glia antigen 2‐expressing stem/progenitor population

Deaths due to end‐stage liver diseases are increasingly registered annually in the world. Liver transplantation is the ultimate treatment for end‐stage liver diseases to date, which has been hampered by a critical shortage of organs. The potential of decellularized liver scaffolds (DLS) derived from solid organs as a three‐dimensional platform has been evolved as a promising approach in liver tissue engineering for translating functional liver organ replacements, but questions still exist regarding the optimal cell population for seeding in DLS and the preparation of the DLS themselves. The aim of our study was to utilize a sodium dodecyl sulfate decellularization procedure in combination with a low concentration of trypsin (0.005%)–ethylenediaminetetraacetic acid (0.002%) process to manufacture DLS from whole mouse livers and recellularized with hepatic stem/progenitors for use in liver tissue engineering and injured liver treatment. Results showed that the DLS generated with all the necessary microstructure and the extracellular components to support seeded hepatic stem/progenitor cell attachment, functional hepatic cell differentiation. Hepatic differentiation from stem/progenitor cells loaded by DLS was more efficient than that of the stem/progenitor cells in the two‐dimensional cell culture model. In summary, the method of DLS loaded by hepatic stem/progenitor cells provided by this study was effective in maintaining DLS extracellular matrix to introduce seeded stem/progenitor cell differentiation, hepatic‐like tissue formation and functional hepatic protein production in vitro that promoted functional recovery and survival in a mouse model of dimethylnitrosamine‐induced liver cirrhosis after auxiliary heterotopic liver transplantation. Copyright © 2016 John Wiley & Sons, Ltd.
Cardiopulmonary Exercise Testing and Metabolic Myopathies

&NA; Skeletal muscle requires a large increase in its ATP production to meet the energy needs of exercise. Normally, most of this increase in ATP is supplied by the aerobic process of oxidative phosphorylation. The main defects in muscle metabolism that interfere with production of ATP are (1) disorders of glycogenolysis and glycolysis, which prevent both carbohydrate entering the tricarboxylic acid cycle and the production of lactic acid; (2) mitochondrial myopathies where the defect is usually within the electron transport chain, reducing the rate of oxidative phosphorylation; and (3) disorders of lipid metabolism. Gas exchange measurements derived from exhaled gas analysis during cardiopulmonary exercise testing can identify defects in muscle metabolism because Symbolo2 and Symbolco2 are abnormal at the level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely diagnosis and guide additional investigation. Defects in glycogenolysis and glycolysis are identified by a low peak Symbolo2 and absence of excess Symbolco2 from buffering of lactic acid by bicarbonate. Defects in the electron transport chain also result in low peak Symbolo2, but because there is an overreliance on anaerobic processes, lactic acid accumulation and excess carbon dioxide from buffering occur early during exercise. Defects in lipid metabolism result in only minor abnormalities during cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and in mitochondrial myopathies, other features may include an exaggerated cardiovascular response to exercise, a low oxygen‐pulse, and excessive ammonia release. Symbol. No caption available.
University students' acceptance of technology in math classes : does gender matter?

Although the Acceptance Technology Model (TAM) has been widely used by researchers to test user's acceptance of technology in education and other domains, research in education have underestimated the role played by gender in determining students' acceptance of technology as part of the educational process. This research study is a unique attempt to explore possible gender differences in university students' perceived acceptance of technology in their mathematics classes. It particularly investigates genders' acceptance to use MyMathLab in university math classes. Structural equation modelling with various constructs was used. Results showed that there is no significant difference between genders on perceived usefulness, subjective norm, attitude, and behavioural intention. However, the effect of perceived ease of use on attitude is significantly higher for male students. The findings have great implications for educators and students as they shed light on the significant factors that determine genders' acceptance of technological tools or platforms used in the math classroom.
Reliability and validity of the 3 Automatic Cognitive Assessment Delivery ( ACAD ) 4 5

Journal Name: Frontiers in Aging Neuroscience ISSN: 1663-4365 Article type: Methods Article Received on: 20 Nov 2013 Accepted on: 19 Feb 2014 Provisional PDF published on: 19 Feb 2014 Frontiers website link: www.frontiersin. org Citation: Di_rosa E, Hannigan C, Brennan S, Reilly R, Rapcan V and Robertson I(2014) Reliability and validity of the Automatic Cognitive Assessment Delivery (ACAD). Front. Aging Neurosci. 6:34. doi:10.3389/fnagi.2014. 00034 Article URL: http://www.frontiersin. org/Journal/Abstract.aspx? s=18& name=aging%20neuroscience&ART_DOI=10.3389/fnagi.2014. 00034
Teachers' Viewpoint on Online Courses

: Many universities that have previously focused on offering blended learning or face to face courses are currently starting to offer more and more also online courses. This paper takes a closer look at the background and perceptions of eight teachers who are about to teach an online course for the first time. More specifically, we take a look at the teachers’ perceptions of themselves as adopters of new pedagogy and new technology as well as their perceptions of strengths and weaknesses of online courses. The preliminary results suggest that our teachers feel rather comfortable with the new technology and especially with the new teaching methods. Most of the teachers identified themselves as innovators or early adopters of new teaching methods. Teachers perceived flexibility and efficiency as the most prevailing strengths of online teaching. On the other hand, weaknesses included workload, technical challenges, and various topics that relate to the lack of face to face interaction. We conclude by discussing what kind of pedagogical support and training the online teachers would benefit from.
Distress intolerance moderation of motivated attention to cannabis and negative stimuli after induced stress among cannabis users: an ERP study

Prevalence of cannabis use is increasing, but many regular users do not develop cannabis use disorder (CUD); thus, CUD risk identification among current users is vital for targeted intervention development. Existing data suggest that high distress intolerance (DI), an individual difference reflective of the ability to tolerate negative affect, may be linked to CUD, but no studies have tested possible neurophysiological mechanisms. Increased motivated attentional processing of cannabis and negative emotional stimuli as indexed by neurophysiology [i.e. the late positive potential (LPP)], particularly during acute stress, may contribute to CUD among high DI users. Frequent cannabis users with high (n = 61) and low DI (n = 44) viewed cannabis, negative, and matched neutral images during electroencephalography (EEG) recording before and after a laboratory stressor. Cannabis cue‐elicited modulation of the 1000‐ to 3000‐milliseconds LPP was larger in high DI users at post‐stressor only, although the effect was only robust in the 1000‐ to 2000‐milliseconds window. Further, modulation magnitude in the high DI group covaried with stress‐relief craving and some CUD indices in the 400‐ to 1000‐milliseconds and 1000‐ to 3000‐milliseconds windows, respectively. No significant effects of DI on negative stimuli‐elicited LPP modulation were found, although inverse associations with some CUD indices were observed. Finally, exploratory analyses revealed some evidence for DI moderation of the relation between subjective stressor reactivity and negative stimuli‐elicited LPP modulation such that greater stressor reactivity was associated with blunted versus enhanced modulation in the high and low DI groups, respectively. Negative and cannabis stimuli‐elicited LPP modulation appear to index distinct, CUD‐relevant neural processes in high DI cannabis users.
Deep 2.5D Vehicle Classification with Sparse SfM Depth Prior for Automated Toll Systems

Automated toll systems rely on proper classification of the passing vehicles. This is especially difficult when the images used for classification only cover parts of the vehicle. To obtain information about the whole vehicle. we reconstruct the vehicle as 3D object and exploit this additional information within a Convolutional Neural Network (CNN). However, when using deep networks for 3D object classification, large amounts of dense 3D models are required for good accuracy, which are often neither available nor feasible to process due to memory requirements. Therefore, in our method we reproject the 3D object onto the image plane using the reconstructed points, lines or both. We utilize this sparse depth prior within an auxiliary network branch that acts as a regularizer during training. We show that this auxiliary regularizer helps to improve accuracy compared to 2D classification on a real-world dataset. Furthermore due to the design of the network, at test time only the 2D camera images are required for classification which enables the usage in portable computer vision systems.
Recent advances in drug and nutrient transport across the blood-retinal barrier

ABSTRACT Introduction: The blood-retinal barrier (BRB) is the barrier separating the blood and neural retina, and transport systems for low-weight molecules at the BRB are expected to be useful for developing drugs for the treatment of ocular neural disorders and maintaining a healthy retina. Areas covered: This review discusses blood-to-retina and retina-to-blood transport of drugs and nutrients at the BRB. In particular, P-gp (ABCB1/MDR1) has low impact on the transport of cationic drugs at the BRB, suggesting a significant role of novel organic cation transporters in influx and efflux transport of lipophilic cationic drugs between blood and the retina. The transport of pravastatin at the BRB involves transporters including organic anion transporting polypeptide 1a4 (Oatp1a4). Recent studies have shown the involvement of solute carrier transporters in the blood-to-retina transport of nutrients including riboflavin, L-ornithine, β-alanine, and L-histidine, implying that dipeptide transport at the BRB is minimal. Expert opinion: Novel organic cation transport systems and the elimination-dominant transport of pravastatin at the BRB are expected to be useful in systemic drug delivery to the neural retina without CNS side effects. The mechanism of nutrient transport at the BRB is expected to provide a new strategy for delivery of nutrient-mimetic drugs.
Reliability and Validity of Work-related Flow Inventory

Objective: To examine the reliabilities and validities of Chinese version of Work-related Flow Inventory(WOLF). Methods: 950 employees in China enterprises were selected and investigated.Results: Exploratory factor analysis showed there were three factors: absorption,work enjoyment and intrinsic work motivation in Chinese version of WOLF.Confirmatory factor analysis on the 3-factor model showed a good fit to the data.Cronbach's α of the whole scale and its subscales were more than 0.70;Two weeks test-retest reliabilities were more than 0.85;Composite reliabilities and average variance extracted from variables were more than 0.80 and 0.50 respectively.Conclusion: With acceptable psychometric quality,the Chinese version of WOLF can be used to measure the flow experience at work of employees in China.
Morphology, Cell Division, and Phylogeny of Uroleptus longicaudatus (Ciliophora, Hypotricha), a Species of the Uroleptus limnetis Complex

A Chinese population of the little‐known freshwater hypotrich Uroleptus longicaudatus was investigated with emphasis on its living morphology and infraciliature. The characteristic, tripartite body consists of a narrowed (cephalized) anterior portion, a slender trunk, and a long, slender, and strongly contractile tail occupying up to 30% of body length. Contracted specimens with a tail length of about 12% closely resemble Uroleptus limnetis which has, like U. longicaudatus, its type locality on the East Coast of the United States so that it cannot be excluded that these two species are synonymous. Thus, we propose to subsume these and few other little‐known species, which are not clearly distinguishable at the present state of knowledge, as U. limnetis complex. The morphogenesis of U. longicaudatus proceeds as in most congeners. The phylogenetic analyses reveal that Uroleptus is a monophyletic group, but due to the lack of detailed morphological data of the populations sequenced so far, the relationships within this taxon remain obscure. For the objective determination of the tail length of hypotrichs, we propose the “1/3‐method”, which says that the tail commences at that body width which corresponds one‐third of the maximum width. Paruroleptus ophryoglena Gelei, 1954 is transferred to Uroleptus: Uroleptus ophryoglena (Gelei, 1954) comb. nov.
Hydrogen Sulfide Reduces Recruitment of CD11b+DG Gr-1+DG Cells in Mice with Myocardial Infarction

The present study aimed to elucidate the mechanisms by which hydrogen sulfide (H2S) attenuates left ventricular remodeling after myocardial infarction (MI). MI was created in mice by left coronary artery ligation. One group of mice received injections of the H2S donor sodium hydrosulfide (NaHS) immediately before and 1 h after ligation, while the control group received saline alone. During both the subacute and chronic stages (1 and 4 weeks postinfarction, respectively), NaHS-treated mice demonstrated attenuation of cardiac dilation in the infarcted myocardium. Furthermore, fewer CD11b+Gr-1+ myeloid cells were detected in the infarct myocardium and peripheral blood from NaHS-treated mice, while more CD11b+ Gr-1+ cells remained in the spleen and bone marrow in these animals. NaHS-treated mice also exhibited reduction in cardiomyocyte apoptosis, interstitial fibrosis, cardiac hypertrophy, and pulmonary edema, as well as overall better survival rates, when compared to controls. Thus, exogenous H2S has favorable effects on cardiac remodeling after MI. These observations further support the emerging concept that H2S treatment might have therapeutic benefits in the setting of ischemia-induced heart failure.
The Effect of Perioperative Fluid Management on Intraocular Pressure during Gynecologic Laparoscopic Pelvic Surgery

Purpose Visual loss is a devastating perioperative complication that can result from elevated intraocular pressure (IOP). The Trendelenburg position during surgery increases IOP. The purpose of this study was to quantify IOP changes in patients undergoing laparoscopic hysterectomy, at different time points and body positions throughout the procedure, and to compare fluctuations of IOP during the perioperative period according to two fluid management protocols. Methods Thirty women scheduled to undergo elective gynecologic laparoscopic pelvic surgery were randomly allocated to receive a liberal or restrictive fluid management protocol. IOP, mean arterial pressure, heart rate, exhaled tidal volume, end-tidal CO2, and ocular perfusion pressure were assessed prior, during, and postsurgery, at 8 time points altogether. Results Mean changes in IOP were similar for the two protocols; the peak IOP was at the steep (peak) Trendelenburg position. For each protocol, IOP correlated positively with mean arterial pressure, and mean blood pressure correlated with ocular perfusion pressure. Conclusion IOP was elevated during laparoscopic pelvic surgery and particularly at the steep Trendelenburg position. No differences were found in any of the parameters examined according to a liberal or restrictive fluid management protocol.