Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium*

Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P1, in lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1 phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1 with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1 attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down-regulation of Spns2 also suppressed HGF-induced lamellipodia formation, suggesting a key role for inside-out S1P signaling. The HGF-mediated phosphorylation of SphK1 and its localization in lamellipodia was dependent on c-Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down-regulation of S1P1, but not S1P2 or S1P3, with specific siRNA attenuated HGF-induced lamellipodia formation. Further, HGF enhanced association of Spns2 with S1P1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF-induced migration of HLMVECs was attenuated by down-regulation of Spns2. Taken together, these results suggest that HGF/c-Met-mediated lamellipodia formation, and perhaps motility is dependent on intracellular generation of S1P via activation and localization of SphK1 to cell periphery and Spns2-mediated extracellular transportation of S1P and its inside-out signaling via S1P1.
Evaluation of a new in-clinic test system to detect feline immunodeficiency virus and feline leukemia virus infection.

BACKGROUND Many in-house tests for the diagnosis of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infection are licensed for use in veterinary practice. A new test with unknown performance has recently appeared on the market. OBJECTIVES The aims of this study were to define the efficacy of a new in-clinic test system, the Anigen Rapid FIV Ab/FeLV Ag Test, and to compare it with the current leading in-clinic test, the SNAP Kombi Plus FeLV Antigen/FIB Antibody Test. METHODS Three-hundred serum samples from randomly selected healthy and diseased cats presented to the Clinic of Small Animal Medicine at Ludwig Maximilian University were tested using both the Anigen Rapid Test and the SNAP Kombi Plus Test. Diagnostic sensitivity, specificity, and positive and negative predictive values were calculated for both tests using Western blot as the gold standard for verification of FIV infection and PCR as the gold standard for FeLV infection. RESULTS The presence of antibodies against FIV was confirmed by Western blot in 9/300 samples (prevalence 3%). FeLV DNA was detected by PCR in 15/300 samples (prevalence 5%). For FIV infection the Anigen Rapid Test had a sensitivity of 88.9%, specificity of 99.7%, positive predictive value of 88.9%, and negative predictive value of 99.7%. For FeLV infection, the Anigen Rapid Test had a sensitivity of 40.0%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 96.9%. Diagnostic accuracy was similar to that of the SNAP Kombi Plus Test. CONCLUSION The new Anigen Rapid FIV Ab/FeLV Ag Test performed very well and can be recommended for use in veterinary practice.
Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles

Asbestos fibers and crystalline silica are carcinogenic to humans when inhaled into the lungs. Asbestos fibers and cigarette smoke most likely act as cofactors in the induction of lung cancer. Point mutations in the K-ras oncogene and the p53 tumor-suppressor gene are frequent in lung cancers and are consistent with the known mutagenic spectrum of tobacco-smoke carcinogens. The FHIT tumor suppressor gene is also frequently inactivated in lung cancers of smokers and in workers who were exposed to asbestos. Recent molecular studies of p53 tumor suppressor gene mutations and p53 protein expression in the lungs of patients with lung cancer and occupational exposure to crystalline silica and other dusts have been conducted. Mutations in the p53 gene were detected at a frequency similar to those in smoking-related lung cancers. Expression of p53 protein can be detected by immunohisto-chemistry in preneoplastic epithelial lesions in the lungs of smokers and workers. Human malignant mesotheliomas frequently show overexpression of p53 protein; however, point mutations at the p53 tumor suppressor gene or ras oncogene locus are rare. Most cases of malignant mesotheliomas have codeletions of the p15 and p16 tumor suppressor genes and alterations at the NF2 tumor suppressor gene locus with monosomy of chromosome 22. The molecular alterations characteristic of malignant mesotheliomas may develop during later stages of tumor progression and may not reflect the direct genotoxic effects of fibers on the target cell population.
Evaluation of the clinical efficacy of multiple lower-extremity nerve decompression in diabetic peripheral neuropathy

Abstract Objective. To evaluate the value of high-resolution ultrasonography and neural electrophysiology in early diagnosis, operative opportunity selection, and clinical effect assessment of DPN. Methods. Five hundred and sixty patients with diabetic peripheral neuropathy (DPN) were treated with DELLON surgical nerve decompression in our hospital in the past 5 years. Before and after 18 months surgery, the tests of the Toronto clinical scoring system, high-resolution ultrasonography, QST, and Nerve Conduction Velocity (NCV) were evaluated in all cases. The control group included 40 diabetic patients in the same age range but without DPN. Results. Ultrasonographic images revealed an apparently normal proximal common peroneal nerve, tibial nerve marked swelling, enlarged, and hypoechogeneity with loss fascicular pattern. The cross-sectional-area, anteroposterior and transverse diameter were measured preoperative and prooperative, and the differences had statistical significance（P < 0.01）. NCV-positive cases amount to 74.9% DPN patients in this study and QST-positive cases amount to 90.9% and had significant differences between them (P < 0.05). Postoperative NCV and cold perception threshold significantly increased (P < 0.05) compared with that of the before surgery. Postoperative warm perception threshold (P < 0.01) and vibration perception threshold (P < 0.05) were significantly lower than the preoperative value. NCV was positively correlated with cold perception threshold (r = 0.395, P < 0.01), and negatively correlated with warm perception threshold (r = − 0.387, P < 0.01) and vibratory perception threshold (r = − 0.367, P < 0.01). The preoperative TCSS score was 19 points for all the cases, and 420 cases (75%) improved to 10–13 points (P < 0.01). Conclusion. Ultrasonography is capable of depicting these nerves morphological information, with respect to exact location, course, and extent. QST is suitable for early diagnosis of DPN, and abnormal QST is an indication of lower extremity nerve decompression for DPN. The joint use of QST and NCV testing helps surgeons to grasp the timing of surgery. High-resolution ultrasound, QST and NCV testing can also be used as an outcome index for surgical treatment.
Intraindividual Variability as a Marker of Neurological Dysfunction: A Comparison of Alzheimer's Disease and Parkinson's Disease

Individuals with certain neurological conditions may demonstrate greater inconsistency (i.e., intraindividual variability) on cognitive tasks compared to healthy controls. Several researchers have suggested that intraindividual variability may be a behavioral marker of compromised neurobiological mechanisms associated with aging, disease, or injury. The present study sought to investigate whether intraindividual variability is associated with general nervous system compromise, or rather, with certain types of neurological disturbances by comparing healthy adults, adults with Alzheimer's disease (AD), and Parkinson's disease (PD). Participants were assessed on four separate occasions using measures of reaction time and memory. Results indicated that inconsistency was correlated with indices of severity of impairment suggesting a dose-response relationship between cognitive disturbance and intraindividual variability: the more severe the cognitive disturbance, the greater the inconsistency. However, participants with AD were more inconsistent than those with PD, with both groups being more variable than the healthy group, even when controlling for group differences in overall severity of cognitive impairment or cognitive decline. Consequently, intraindividual variability may index both the severity of cognitive impairment and the nature of the neurological disturbance.
A study of the expectations on the use of social assistive robots and telehealthcare systems

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Attachment Style Changes Following Intensive Short-term Group Psychotherapy

In this study, we examined changes in attachment style as measured by the Relationship Scales Questionnaire before and after six weeks of intensive group psychotherapy. We also investigated whether changes in attachment style were associated with changes in interpersonal functioning. Results indicated that participants showed increases in secure attachment and decreases in fearful attachment and, to a lesser degree, preoccupied attachment styles. Change was not found in the dismissive attachment style. Changes in Secure and/or Fearful (but not Preoccupied) attachment styles were related to changes in interpersonal functioning on seven of the eight subscales of the Inventory of Interpersonal Problems. Overall findings suggest intensive group psychotherapy programs show promise for reducing attachment pathology and improving interpersonal functioning. Assessing differential responsiveness to psychotherapy may help us align our interventions to better address differing attachment styles through modifications in focus and approach.
Symptom Resolution and Patient-Perceived Recovery Following Ankle Arthroplasty and Arthrodesis

Background: Patients’ perception of outcomes is not always defined by the absence of limitations/symptoms (resolution), but can also be characterized by behavioral adaptation and cognitive coping arising in cases with residual deficits. Patient-reported outcome measures (PROs) are designed to measure levels of function or symptoms, largely missing whether patients are coping with ongoing limitations. This study aimed to broaden the conventional definition of a “satisfactory” outcome following ankle reconstruction by comparing patient-reported outcomes of patients with and without residual symptoms and limitations. Methods: The study consisted of a cross-sectional survey of ankle arthroplasty (n = 85) and arthrodesis (n = 15) patients. Outcome measures included the Ankle Osteoarthritis Scale, Short Musculoskeletal Function Assessment, Short Form-12, and EuroQol-5 Dimension. Patients also completed measures of pain (0-10), stiffness (0-10), satisfaction (0-3), and ability to complete activities of daily living (ADL) (0-6). Based on a self-reported question regarding recovery and coping, patients were categorized as “Recovered-Resolved” (better with no symptoms or residual effects), “Recovered, not Resolved” (RNR, better with residual effects), or “Not Recovered” (not better). Recovery groups were compared across measures. Results: Only 15% of patients were categorized Recovered-Resolved. Most were RNR (69%), leaving 14% Not Resolved. Recovered-Resolved experienced lower rates of pain (1.4 ± 2.3), stiffness (1.1 ± 2.6), and difficulty performing ADLs (0.9 ± 1.2). Overall, outcome measure scores were high (ie, better health) for Recovered-Resolved patients, midrange for RNR patients, and low for Not Recovered patients, thus confirming predefined hypotheses. Recovered-Resolved and RNR patients had similarly high satisfaction summary scores (3.0 ± 0.0 vs 2.6 ± 0.6). Conclusion: Most patients reported positive outcomes, but few (15%) experienced resolution of all symptoms and limitations. Current PROs focus on achieving low levels of symptoms and limitations, but miss an important achievement when patients are brought to a level of residual deficits with which they can cope. Patients’ perceptions of satisfactory outcomes were not predicated on the resolution of all limitations; thus, the conventional definition of “satisfactory” outcomes should be expanded accordingly. Level of Evidence: Level II, prospective cohort study.
Antihypertensive treatment during pregnancy and functional development at primary school age in a historical cohort study

Please cite this paper as: Pasker‐de Jong P, Zielhuis G, van Gelder M, Pellegrino A, Gabreëls F, Eskes T. Antihypertensive treatment during pregnancy and functional development at primary school age in a historical cohort study. BJOG 2010;117:1080–1087.
The effect of tumor CEA content and tumor size on tissue uptake of indium 111‐labeled anti‐CEA monoclonal antibody

This study was undertaken to determine the effect of tumor size and tumor carcinoembryonic antigen (CEA) content on the uptake of indium 111 (111In)‐labeled anti‐CEA monoclonal antibody in nude mice bearing xenografts. The tumor cell lines were WiDr, SW403, and LS174T, human colon cancer derivatives. The murine breast carcinoma cell line EMT‐6 was used as a control. Tumor CEA levels (ng/g) of tumor standard error of the mean [SEM], measured by enzyme immunoassay (EIA) were: EMT‐6, 0; WiDr, 105 ± 5.7; LS174T, 2052 ± 198; SW403, 17,575 ± 1,785. The 111In‐labeled monoclonal antibody was injected intravenously into mice bearing a single tumor. At 48 hours postinjection, scintiscan was performed, and the mice were killed so that biodistribution studies could be performed. The uptake of the monoclonal antibody was expressed as percent injected counts per minute per gram of tissue ± SEM. The non‐CEA‐producing tumor, EMT‐6, showed the lowest tumor uptake (1.4 ± 0.3). WiDr, an intermediate CEA‐producing tumor, showed some tumor uptake (16.4 ± 1.5). The high CEA‐producing tumors, SW403 and LS174T, had high tumor uptake (29.5 ± 5.0 and 51.1 ± 6.1, respectively). Biodistribution and scintiscan quality were closely related. Although LS174T had the best tumor uptake, SW403 had the highest CEA tumor content, indicating tumor CEA content cannot entirely predict scintiscan and biodistribution results. Tumor‐to‐blood (T/B), tumor‐to‐liver (T/L), and liver‐to‐blood (L/B) ratios were calculated for each animal and compared with tumor size. It was found that T/L had a negative correlation with tumor size (r = −0.72) and L/B had a positive correlation with tumor size (r = 0.94). These ratios may be useful clinically to follow response to therapy.
Characteristics of Patients with Primary Acute Lateral Patellar Dislocation and Their Recovery within the First 6 Months of Injury

We prospectively studied the characteristics and early recovery of an unselected population of patients who had acute first-time lateral patellar dislocation. The recovery program used standardized rehabilitation, emphasizing range of motion, muscle strength, and return of function. Patients returned to stressful activities including sports as tolerated when they regained full passive range of motion, had no effusion, and when quadriceps muscle strength was at least 80% compared with the noninjured limb. Seventy-four patients met the enrollment criteria; 37 men and 37 women. The average age was 19.9 years, and preinjury sports participation was similar to that of ligament-injury patients. Four percent of patients (N 3) had a history of birth complications, 3% (N 2) had a history of lower extremity problems as an infant or child, and 9% (N 7) had a family history of patellar dislocation. Radiographs revealed a 50% incidence (N 37) of patella alta; all patients demonstrated lateral patellar overhang. Patients regained range of motion (mean, 0° to 132°) by 6 weeks. Sports participation remained significantly reduced throughout the first 6 months after injury, with the greatest limitations in kneeling and squatting. At 6 months, 58% of patients (N 43) noted limitation in strenuous activities. The patients who had acute primary patellar dislocation were young and active. Most injuries occurred during sports, and few patients had abnormal physical features, contradicting any stereotype of an overweight, sedentary, adolescent girl whose patella dislocates with little or no trauma.
A new quality assessment parameter for optical coherence tomography

Aim: To create a new, automated method of evaluating the quality of optical coherence tomography (OCT) images and to compare its image quality discriminating ability with the quality assessment parameters signal to noise ratio (SNR) and signal strength (SS). Methods: A new OCT image quality assessment parameter, quality index (QI), was created. OCT images (linear macular scan, peripapillary circular scan, and optic nerve head scan) were analysed using the latest StratusOCT system. SNR and SS were collected for each image. QI was calculated based on image histogram information using a software program of our own design. To evaluate the performance of these parameters, the results were compared with subjective three level grading (excellent, acceptable, and poor) performed by three OCT experts. Results: 63 images of 21 subjects (seven each for normal, early/moderate, and advanced glaucoma) were enrolled in this study. Subjects were selected in a consecutive and retrospective fashion from our OCT imaging database. There were significant differences in SNR, SS, and QI between excellent and poor images (p = 0.04, p = 0.002, and p<0.001, respectively, Wilcoxon test) and between acceptable and poor images (p = 0.02, p<0.001, and p<0.001, respectively). Only QI showed significant difference between excellent and acceptable images (p = 0.001). Areas under the receiver operating characteristics (ROC) curve for discrimination of poor from excellent/acceptable images were 0.68 (SNR), 0.89 (IQP), and 0.99 (QI). Conclusion: A quality index such as QI may permit automated objective and quantitative assessment of OCT image quality that performs similarly to an expert human observer.
Understanding the Intention of Using Mobile Social Networking Apps Across Cultures

ABSTRACT Understanding the user acceptance of mobile social networking apps in different cultures can provide powerful insights for managers and marketers of social networking apps to develop effective globalized and localized strategies to attract users worldwide. Following the theory of planned behavior, this study develops a research model of privacy concern (PC), privacy risk (PR), and perceived enjoyment (PE) as attitudinal beliefs, subjective norm (SN) as normative belief, and smartphone self-efficacy (SE) as control belief to understand users’ intention to use mobile social networking apps. In particular, the impact of culture was investigated, considering the user base of mobile social networking apps is distributed globally and culturally diversified, and cultural values have direct impact on behavior. The research model was validated by survey data collected from 151 participants in the U.S. and 170 participants in South Korea. The data analysis results show that perceived enjoyment and subjective norm are the most important drivers behind users’ intention to use mobile social networking apps for both countries. No significant difference was found for the effects of privacy risk and subjective norm upon users’ intention to use mobile social networking apps across cultures. Implications of the findings upon theory and practice are discussed.
Dendritic growth gated by a steroid hormone receptor underlies increases in activity in the developing Drosophila locomotor system

Significance Why do bigger animals have bigger brains, and how do they get them? We find in Drosophila larvae that motoneuron dendrites, the branched structures receiving information from other neurons, grow as the animal gets bigger, and that this is regulated on a cell-by-cell basis by a specific isoform of a steroid hormone receptor, whose functions were unknown. As these dendrites enlarge, they form more connections with presynaptic partners, leading to greater levels of neuronal activity. We propose that these nerve cells increase their activity to compensate for the demands of a bigger body. As animals grow, their nervous systems also increase in size. How growth in the central nervous system is regulated and its functional consequences are incompletely understood. We explored these questions, using the larval Drosophila locomotor system as a model. In the periphery, at neuromuscular junctions, motoneurons are known to enlarge their presynaptic axon terminals in size and strength, thereby compensating for reductions in muscle excitability that are associated with increases in muscle size. Here, we studied how motoneurons change in the central nervous system during periods of animal growth. We find that within the central nervous system motoneurons also enlarge their postsynaptic dendritic arbors, by the net addition of branches, and that these scale with overall animal size. This dendritic growth is gated on a cell-by-cell basis by a specific isoform of the steroid hormone receptor ecdysone receptor-B2, for which functions have thus far remained elusive. The dendritic growth is accompanied by synaptic strengthening and results in increased neuronal activity. Electrical properties of these neurons, however, are independent of ecdysone receptor-B2 regulation. We propose that these structural dendritic changes in the central nervous system, which regulate neuronal activity, constitute an additional part of the adaptive response of the locomotor system to increases in body and muscle size as the animal grows.
Influence of Frequency Dependent Time to Breakdown on High-K/Metal Gate Reliability

Time-dependent dielectric breakdown and stress-induced leakage current (SILC) behavior of a 28-nm hafnium-based high-k/metal gate n-type MOS transistors are investigated under dc and ac conditions. Compared with the constant voltage stress results under dc conditions, a decrease in device lifetime is observed for low-frequency ac stress. Degradation enhancement and SILC behavior are attributed to defect generation in the SiO2 interface layer. For high-frequency ac stress, a lifetime improvement is observed, because of reduced trap generation.