Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet‐Rich Plasma Greatly Potentiates Insulin‐Induced Adipogenic Differentiation of Human Adipose‐Derived Stem Cells Through a Serine/Threonine Kinase Akt‐Dependent Mechanism and Promotes Clinical Fat Graft Maintenance

The potential plasticity and therapeutic utility in tissue regeneration of human adipose‐derived stem cells (ASCs) isolated from adult adipose tissue have recently been highlighted. The use of autologous platelet‐rich plasma (PRP) represents an alternative strategy in regenerative medicine for the local release of multiple endogenous growth factors. Here we investigated the signaling pathways and effects of PRP and human recombinant insulin on proliferation and adipogenic differentiation of ASCs in vitro. PRP stimulated proliferation (EC50 = 15.3 ± 1.3% vol/vol), whereas insulin's effect was the opposite (IC50 = 3.0 ± 0.5 μM). Although PRP alone did not increase adipogenesis, in association with insulin it prevented ASC proliferative arrest, greatly enhanced intracytoplasmic lipid accumulation, strongly increased serine/threonine kinase Akt phosphorylation and mouse monoclonal anti‐sterol regulatory element binding protein‐1 accumulation, and downregulated Erk‐1 activity; adipogenic effects were markedly prevented by the Akt inhibitor wortmannin. PRP with insulin synergistically upregulated fibroblast growth factor receptor (FGFR) and downregulated epidermal growth factor receptor (ErbB) expression; moreover, PRP in association prevented insulin‐induced insulin‐like growth factor‐1 receptor and insulin receptor downregulation. The inhibition of FGFR‐1, epidermal growth factor receptor (EGFR), and epidermal growth factor receptor‐2 (ErbB2) activity reduced ASC proliferation, but only that of FGFR‐1 reduced adipogenesis and Akt phosphorylation, whereas the ErbB2 inhibition effects were the opposite. However, EGFR activity was needed for ErbB2‐mediated inhibition of ASC adipogenesis. Clinically, the injection of insulin further ameliorated patients' 1‐year PRP‐induced fat graft volume maintenance and contour restoring. Our results ascertain that PRP in association with insulin greatly potentiates adipogenesis in human ASCs through a FGFR‐1 and ErbB2‐regulated Akt mechanism. The ameliorated clinical fat graft maintenance suggests additional useful translational applications of combined PRP‐insulin treatment in regenerative medicine.
Prophylactic implantable cardioverter-defibrillator treatment in the elderly: therapy, adverse events, and survival gain.

AIMS In elderly patients, obscurity remains regarding the benefit of implantable cardioverter-defibrillator (ICD) treatment as primary prevention of sudden cardiac death. This study assesses implant rates, therapy, adverse events, and survival gain in the elderly primary prevention ICD patient. METHODS AND RESULTS A total of 1395 patients treated with an ICD for primary prevention of sudden cardiac death at the Leiden University Medical Center were included and allocated to three groups according to age. Endpoints consisted of appropriate shocks and survival gain, defined as the time following first appropriate ICD shock to death. Mean follow-up was 2.9 ± 2.1 years. Fifty-one per cent of the patients were <65 years, 35% were 65-74 years, and 14% were ≥75 years. Prior to the year 2000, no ICDs were implanted in patients ≥75 years; 29% of the ICDs were implanted in patients 65-74 years. After 2005, 53% of the ICD recipients were ≥65 years at the time of implant, including 16% aged ≥75 years (P = 0.03). Five-year cumulative incidence of appropriate shocks was 19% for patients <65 years, 23% for patients 65-74 years, and 13% for patients ≥75 years (P = 0.47). At 1-year following appropriate shock, cumulative incidence for death was 35% for patients ≥75 years as compared with 7% for patients <65 years (P < 0.01). CONCLUSION In routine clinical practice, the percentage of patients ≥75 years receiving an ICD for primary prevention is increasing. Despite experiencing comparable rates of appropriate ICD shocks, life prolongation by ICD is significantly less in elderly as compared to younger patients.
Is the one‐step nucleic acid amplification assay better for intra‐operative assessment of breast sentinel nodes?

Intra‐operative assessment of sentinel lymph nodes in breast cancer offers the opportunity to prevent two‐stage surgical procedures. At our institution we employ touch imprint cytology (TIC), which lacks sensitivity. In this study we compare the one‐step nucleic acid amplification (OSNA) assay to TIC.
Reactive Oxygen Species (ROS) Mediate p300-dependent STAT1 Protein Interaction with Peroxisome Proliferator-activated Receptor (PPAR)-γ in CD36 Protein Expression and Foam Cell Formation*

Background: CD36 plays a role in lipid uptake, foam cell formation, and atherogenesis. Results: 15(S)-HETE induces CD36 expression and foam cell formation by triggering p300-mediated STAT1 acetylation and its interaction with PPARγ. Conclusion: STAT1 and PPARγ interact with each other in CD36 expression and foam cell formation. Significance: 15(S)-HETE appears to play an important role in foam cell formation, a critical event in atherogenesis. Previously, we have demonstrated that 15(S)-hydroxyeicosatetranoic acid (15(S)-HETE) induces CD36 expression involving STAT1. Many studies have shown that peroxisome proliferator-activated receptor (PPAR)-γ mediates CD36 expression. Therefore, we asked the question whether these transcriptional factors interact with each other in the regulation of CD36 expression by 15(S)-HETE. Here, we show that STAT1 interacts with PPARγ in the induction of CD36 expression and foam cell formation by 15(S)-HETE. In addition, using molecular biological approaches such as EMSA, supershift EMSA, ChIP, re-ChIP, and promoter-reporter gene assays, we demonstrate that the STAT1 and PPARγ complex binds to the STAT-binding site at −107 nucleotides in the CD36 promoter and enhances its activity. Furthermore, the interaction of STAT1 with PPARγ depends on STAT1 acetylation, which is mediated by p300. In addition, our findings show that reactive oxygen species-dependent Syk and Pyk2 stimulation is required for p300 tyrosine phosphorylation and activation. Together, these results demonstrate that an interaction between STAT1, p300, and peroxisome proliferator-activated receptor-γ is required for 15(S)-HETE-induced CD36 expression, oxidized low density lipoprotein uptake, and foam cell formation, critical events underlying the pathogenesis of atherosclerosis.
Different Carboxyl-terminal Domain Kinase Activities Are Induced by Heat-shock and Arsenite.

In response to heat-shock and chemical treatments, cells undergo profound biochemical changes such as modifications in protein phosphorylation in order to resist the new, unfavorable growth conditions. We have previously shown that in HeLa cells a protein kinase (HS-CTD kinase) activity is induced rapidly after a heat or sodium arsenite shock. This kinase activity is able to phosphorylate a synthetic peptide composed of four repeats of the motif Ser-Pro-Thr-Ser-Pro-Ser-Tyr, a motif highly repeated in the carboxyl-terminal domain (CTD) of the largest subunit of eukaryotic RNA polymerase II. In this paper, we designed a new experimental procedure to characterize the substrate specificity of this kinase activity. We show that HS-CTD kinase activity phosphorylates a consensus sequence (-P-X-S/T-P-) which is similar to the sequence phosphorylated by extracellular regulated protein kinases (also called mitogen-activated protein kinases). However, there is a slight but reproducible difference between these kinases in their use of serine or threonine as the phosphate acceptor. Mono Q chromatography allows the separation of five stress-induced CTD kinase activities, two of which coelute with active mitogen-activated protein kinase forms revealed by Western blotting with anti ERK1-ERK2 antibodies. The other three CTD kinase activities induced after a stress are distinct from ERK1 and ERK2 and have different enzymatic properties. The molecular nature of these HS-CTD kinases and the physiological significance of their activation during stress remain to be determined.
Effect of the neuropeptide substance P on the rat bone marrow‐derived osteogenic cells in vitro

Substance P containing, thin, sensory nerve fibres have been demonstrated in bone and bone marrow. However the role of substance P in bone tissue is not fully understood. We investigated the effects of substance P on the growth and development of rat bone marrow‐derived osteogenic cells in vitro. To examine this, the marrow‐derived osteogenic cells were treated from 3rd to 6th day of subculture with substance P at concentrations 10−10, 10−9 and 10−8M. [3H]‐thymidine, L‐2,3‐[3H]‐proline incorporation, protein accumulation, alkaline phosphatase activity, and calcium deposition were measured in cultures. Substance P slightly stimulated [3H]‐thymidine incorporation at 10−10 M. Protein accumulation and L‐2,3‐[3H]‐proline incorporation were enhanced in a dose dependent manner. Simultaneous application of spantide, a substance P receptor antagonist, could not block substance P‐induced L‐2,3‐[3H]‐proline incorporation probably because of statistically significant effect of spantide itself. Calcium deposits were significantly lower (about 30%) in cultures treated with SP. This effect was probably due in part by the fall in alkaline phosphatase activity which in substance P treated cultures was decreased about 17%. Our results indicate that substance P could be one of the factors modulating bone metabolism. J. Cell. Biochem. 81:499–506, 2001. © 2001 Wiley‐Liss, Inc.
Abnormal DNA patterns in animal mitochondria: ethidium bromide-induced breakdown of closed circular DNA and conditions leading to oligomer accumulation.

Treatment of cultured mouse fibroblasts (L-cells) and hamster kidney cells with ethidium bromide was found to inhibit the incorporation of [(3)H]thymidine into mitochondrial closed-circular DNA, but not into nuclear DNA. The specific activity of nuclear DNA in treated cells was higher than in control cells. Treatment also led to breakdown of closed-circular mitochondrial DNA, greatly enlarged mitochondrial profiles with few or no cristae, and a higher yield of mitochondrial protein per cell.A significant increase in the content of circular DNA dimers and oligomers of mitochondria was observed after treatment of L-cells with cycloheximide and puromycin or treatment of chick fibroblasts with cycloheximide, and in hamster kidney cells transformed with polyoma virus. Little or no effects on dimer and oligomer content were found in L-cells treated with vinblastine, colcemid, rifampicin, chloramphenicol, or mengovirus, in Rous-transformed hamster cells, or in cuprizone-induced giant mitochondria of rat liver.
A Robust Technique for Single-Phase Grid Voltage Fundamental and Harmonic Parameter Estimation

This paper reports a frequency-adaptive robust technique for the accurate estimation of the single-phase grid voltage fundamental and harmonic parameters. The technique is based on the discrete Fourier transform and a cascaded delayed signal cancellation strategy. There is no stability issue in the technique, since it does not contain any type of feedback loop. It can also be flexibly configured to estimate the parameters of the fundamental and/or one/multiple harmonic(s) from the grid voltage waveform distorted by various harmonics. Moreover, it does not require evaluation of trigonometric and inverse trigonometric functions for implementing on real-time digital signal processor. However, it needs computationally demanding high-order finite-impulse-response filters. The simulation and real-time experimental results are provided to verify the performance of the proposed technique.
Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals.

SCOPE Vitamin D₃, its biologically most active metabolite 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and the vitamin D receptor (VDR) are important for adipose tissue biology. METHODS AND RESULTS We extrapolated genomic VDR association loci in adipocytes from 55 conserved genome-wide VDR-binding sites in nonfat tissues. Taking the genes DUSP10, TRAK1, NRIP1, and THBD as examples, we confirmed the predicted VDR binding sites upstream of their transcription start sites and showed rapid mRNA up-regulation of all four genes in SGBS human pre-adipocytes. Using adipose tissue biopsy samples from 47 participants of a 5-month vitamin D₃ intervention study, we demonstrated that all four primary VDR target genes can serve as biomarkers for the vitamin D₃ responsiveness of human individuals. Changes in DUSP10 gene expression appear to be the most comprehensive marker, while THBD mRNA changes characterized a rather different group of study participants. CONCLUSION We present a new approach to predict vitamin D target genes based on conserved genomic VDR-binding sites. Using human adipocytes as examples, we show that such ubiquitous VDR target genes can be used as markers for the individual's response to a supplementation with vitamin D₃.
Comparison of Results between the Miniature FASat-Bravo Ozone Mapping Detector (OMAD) and NASA’s Total Ozone Mapping Spectrometer (TOMS)

The Ozone Layer Monitoring Experiment (OLME) on board the FASat-Bravo microsatellite launched in July 1992 observed backscattered UV to retrieve atmospheric ozone using two instruments: the Ozone Ultraviolet Backscatter Imager (OUBI) and the Ozone Mapping Detector (OMAD). Initial results from this experiment have shown good qualitative agreement with data from NASA’s TOMS instrument [1]. More recent studies of OMAD data have found quantitative agreement in their radiances and even indicated detection of a volcanic eruption plume from the Nyamuragira volcano [2].
Have Chinese Firms Become Smaller? If So, Why?

Normally as an economy develops, firm sizes increase. However, as measured by the employment rate, the firm size in China declined from 2004 to 2008. In this paper, we develop a structural dynamic model with heterogeneous workers to study the relative contributions of three factors to declining firm size: rising real wages, implementation of minimum wages, and the introduction of a new national labor contract law. While rising wages make a sizeable contribution, we find that the new labor law plays a dominant role in solving the puzzle. In comparison, the impact of minimum wages is more muted.
Patterns of power mower injuries in children compared with adults and the elderly.

Power mower trauma remains an alarmingly frequent cause of serious injury in young children. The patterns of mower-related injuries in children < 15 years old (n = 13) were compared with those of adults aged 15-64 (n = 16) and elderly victims > or = 65 years old (n = 6), who were similarly injured over the past 5 years. Children were more likely to be injured in accidents involving high-energy riding mowers. Of those children injured, 69% (9 of 13) were playing in the yard while 31% (4 of 13) were riding on the mower with a guardian when the injury occurred. Amputations in children were more frequent and more extensive than in the adults and included one forearm, two Symes, and three below-knee amputations. The need for transfusion was also significantly increased in children (62% vs. 6% adults, p < 0.005), who were also more likely to require prolonged hospitalization (11.8 days vs. 5 days in adults, p < 0.005). Aggressive efforts to increase public awareness regarding the cause and nature of power mower injuries are warranted to decrease the incidence of this debilitating but preventable trauma in young children.
MR imaging of hepatic metastases caused by neuroendocrine tumors: comparing four techniques.

OBJECTIVE The aim of our prospective study was to assess the MR imaging characteristics of hepatic metastases of neuroendocrine tumors and to determine the optimal MR sequence for their detection. SUBJECTS AND METHODS Thirty-seven consecutive patients with liver metastases from neuroendocrine tumors underwent 1.5-T MR imaging of the liver comprising T2-weighted fast spin-echo with respiratory monitoring, breath-hold T2-weighted single-shot fast spin-echo, and T1-weighted gradient-recalled echo sequences before and after the injection of gadoterate dimeglumine. Images were reviewed independently by three observers for the number, location, and pattern of signal and enhancement of metastases. RESULTS A total of 359 metastases were detected, 279 on T2-weighed fast spin-echo, 231 on T2-weighed single-shot fast spin-echo, 272 on unenhanced T1-weighted, 322 on hepatic arterial phase, and 228 on portal venous phase images. Hepatic arterial phase images revealed the greatest number of metastases in 70% of patients, including 35 metastases seen only on this sequence, and was significantly superior to the unenhanced T1-weighted and portal venous phase sequences (p < 0.01). The lesion-to-liver contrast was significantly greatest with T2-weighed fast spin-echo sequences. The enhancement patterns of metastases were predominantly hypervascular, hypovascular, peripheral with progressive fill-in, and delayed in, respectively, 27, four, four, and two patients. Most metastases with peripheral enhancement and progressive fill-in were heterogeneous on T2-weighted images and were without globular peripheral enhancement. CONCLUSION Hepatic metastases of neuroendocrine tumors had a typical hypervascular pattern in 73% of patients. Hepatic arterial phase and fast spin-echo T2-weighed sequences are the most sensitive.
Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct‐Acting Antiviral Agents

The direct‐acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end‐stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon‐free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy‐proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon‐based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment‐related side effects.
Pathological features of colorectal carcinomas in MYH‐associated polyposis

Aims: MYH is a DNA glycosylase in the base excision repair pathway. Germ‐line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics.
Melodic Segmentation on Different Musical Genres

To create a sufficient repository of test data for our model-based implementations of music information retrieval functions working on symbolic documents, we have used three different approaches to melodic segmentation on monophonic pieces with a broad range of genres from baroque/classical music to pop/rock. All three methods are driven by musical knowledge (in contrast to methods such as n-gram segmentation). Two of the algorithms we have applied are taken from former work of other researchers, the third algorithm has been developed in our department and will be introduced briefly. Our repository of test documents (midi format) consisted of 52 files making it more representative (2.5 to 5 times the number of documents)than those that have been referenced in previous publications. This paper describes our experiences with the applied algorithms, the results that have been achieved, and the conclusions we have been able to draw for improving music segmentation methods.
A Prospective Study of Injury Patterns in Collegiate Pole Vaulters

Background: Although pole vaulting has been a sanctioned collegiate event since the 1920s, little is known about the injury patterns observed in the sport. Purpose: To describe injury incidence, patterns, and risks in collegiate pole vaulters. Study Design: Descriptive epidemiology study. Methods: This was a prospective cohort study of collegiate athletes participating in pole vault over a single track-and-field season. Baseline athlete information was collected on study enrollment. Injuries were recorded in a standardized form to document diagnosis and event circumstances. A log of practice and competition exposures was maintained for each athlete. Injury incidence was reported as the proportion of injured vaulters and number of new injuries per 1000 athlete-exposures. Regression analysis on baseline variables was performed to determine risks for injury. Results: A total of 135 vaulters from 15 universities took part in the study. There were 70 injury events reported during 8823 exposures. Forty-one percent of vaulters sustained injury, and there were 7.9 injuries per 1000 athlete-exposures. The low back was the most common injury location (16.7%), followed by the hamstrings and lower leg (13.9% each). Overall, 60% of injuries were to the lower extremities, 21% to the upper extremities, and 18% to the back. No head or neck injuries were reported. Injuries were most commonly muscular strains (39.2%) or overuse type (25.5%). Thirty percent, including 83% of low back injuries, occurred during the plant/takeoff phase of the vault. One-third of lumbar injuries were spondylolysis, with 75% of these being season ending. The odds of injury were 2.7 (95% CI, 1.1-7.1) times greater in vaulters with multiple prior injuries. Conclusion: This is the first prospective study of injury patterns in collegiate pole vaulters. The results indicate that injuries are very common in experienced vaulters. Medical personnel and coaches should be aware of the propensity for overuse-type injuries and institute activity modification to reduce time lost. In addition, coaches and athletes should focus on proper technique, particularly during the plant/takeoff to help minimize back injury. Medical providers should maintain a high level of suspicion for symptomatic spondylolysis in any vaulter complaining of frequent or persistent low back pain. Detailed medical histories are important to identify prior injuries, and coaches should focus on changing technical flaws or behaviors that may contribute to reinjury.