Miracle-dz/UniFAR-FTUs huggingface dataset:
The PI3K/AKT Signaling Pathway Controls the Quiescence of the Low‐Rhodamine123‐Retention Cell Compartment Enriched for Melanoma Stem Cell Activity

Melanoma is one of the most aggressive and extremely resistant to conventional therapies neoplasms. Recently, cellular resistance was linked to the cancer stem cell phenotype, still controversial and not well‐defined. In this study, we used a Rhodamine 123 (Rh123) exclusion assay to functionally identify stem‐like cells in metastatic human melanomas and melanoma cell lines. We demonstrate that a small subset of Rh123‐low‐retention (Rh123low) cells is enriched for stem cell‐like activities, including the ability to self‐renew and produce nonstem Rh123high progeny and to form melanospheres, recapitulating the phenotypic profile of the parental tumor. Rh123low cells are relatively quiescent and chemoresistant. At the molecular level, we show that melanoma Rh123low cells overexpress HIF1α, pluripotency factor OCT4, and the ABCB5 marker of melanoma stem cells and downregulate the expression of Cyclin D1 and CDK4. Interestingly, a short treatment with LY294002, an inhibitor of the PI3K/AKT pathway, specifically reverts a subset of Rh123high cells to the Rh123low phenotype, whereas treatment with inhibitors of mammalian target of rapamycin, phosphatase and tensin homolog or mitogen‐activated protein kinase signaling does not. This phenotypic switching was associated with reduced levels of the HIF1α transcript and an increase in the level of phosphorylated nuclear FOXO3a preferentially in Rh123low cells. Moreover, the Rh123low cells became less quiescent and displayed a significant increase in their melanosphere‐forming ability. All the above indicates that the Rh123low melanoma stem cell pool is composed of cycling and quiescent cells and that the PI3K/AKT signaling while maintaining the quiescence of Rh123low G0 cells promotes the exit of cycling cells from the stem cell compartment. STEM CELLS 2013;31:641–651
CXCL13 (BCA‐1) is produced by follicular lymphoma cells: role in the accumulation of malignant B cells

Summary. Follicular lymphomas (FLs) localize in lymphoid tissues and recapitulate the structure of normal secondary follicles. The chemokine/chemokine receptor pair CXCL13/CXCR5 is required for the architectural organization of B cells within lymphoid follicles. In this study, we showed that CXCL13 was secreted by FL cells. FL cells expressed CXCR5 and migrated in response to CXCL13. Furthermore, we observed a synergistic effect between CXCL13 and CXCL12 (SDF‐1), a chemokine produced by stromal cells in lymphoid tissues. The production of CXCL13 by FL cells and CXCL12 by stromal cells probably directs and participates in the accumulation of FL cells within specific anatomic sites.
Matrix Metalloproteinases and Atherogenesis in Dependence of Age

Background: Changes in the proteoglycan metabolism of the intima of arteries belong to the initial lesions of atherosclerosis (AS). The accumulation of proteoglycans, alterations of pericellular glycoproteins and modulations of collagen turnover also play a fundamental role in the progression of AS. They influence lipid retention, cell behavior and calcinosis. The decisive role played by the matrix metalloproteinases (MMPs) and their inhibiting factors (tissue inhibitors of metalloproteinases [TIMPs]) in these processes is not yet fully understood and therefore the subject of this overview. The causes of the abrupt change of a long-term existing stabile AS to a vulnerable plaque as well as the participation of age-related vascular wall remodeling in the progression of AS also remain open questions. Discussion: Apart from the well-known risk factors for AS, less well-known influences like the disturbances of gene expression in vascular smooth muscle cells affect an MMP/TIMP imbalance. The various consequences of this imbalance range from intima cell proliferation as an early change in AS as well as accelerated progression to the destabilization of fibrous plaques by increased collagenolysis as well as the formation of aneurysms. Infectious or toxic influences may trigger these mechanisms; an involvement of age-related vessel wall changes should also be considered. The prognostic significance of circulating MMP concentrations for the existence of instabile plaques are of great interest, as is the plaque stabilizing effect of statins by suppression of MMPs. Conclusions: MMPs navigate the behavior of vascular wall cells in different AS stages, in adaptive remodeling, in normal aging and in non-atherosclerotic vessel disease. The clinical relevance of a disturbance in the MMP/TIMP balance is demonstrated firstly by the initiation of AS due to migration and proliferation of intima cells and secondly in the collagenolysis, necrotic transformation and apoptosis of existing fibrous lesions resulting in instabile rupture proned plaques. Investigations into the genetic typing of MMPs and the results of experimental gene deficiency models have significantly contributed to the clarification of these facts.
Previous Open Renal Surgery Increased Vascular Complications in Percutaneous Nephrolithotomy (PCNL) Compared with Primary and Secondary PCNL and Extracorporeal Shock Wave Lithotripsy Patients: A Retrospective Study

Objective: To evaluate the vascular complications of percutaneous nephrolithotomy (PCNL) patients who have undergone previous open surgery, PCNL and extracorporeal shock wave lithotripsy (ESWL). Patients and Methods: 360 patients who underwent a PCNL procedure were included into the study. The patients were divided into 4 groups: group 1: primary PCNL (n = 232); group 2: previous open nephrolithotomy (n = 42); group 3: previous PCNL (n = 33); group 4: previous ESWL (n = 63). The periods of operation and fluoroscopy use of the groups were compared in terms of residual stones, with haematuria, pre-operation and post-operation first-day haemoglobin values. Patients with persistent haematuria were assessed through ultrasonography (US), Doppler US, computed tomography and angiography. Results: Upon comparison of the patients' pre- and post-operative haemoglobin changes, haemoglobin was statistically higher in the previous open operation group than the others (p = 0.02). Permanent and intermittent haematuria were detected in 12 (3%) and 7 patients (1%), respectively. Angiography was done in 7 (1.94%) patients. This rate was 9.5% for group 2 and 3% for group 3. These rates were found to be statistically higher than compared to the other groups. Arteriovenous fistula (AVF) was detected in 4 of these patients and pseudoaneurysm in 1. While 1 of the patients with AVF improved spontaneously, embolisation was applied to 4 patients. Four of the patients had had a previous open operation, while 1 had had a PCNL treatment. Conclusions: Vascular complication is a rare complication of PCNL that can be successfully managed with angioembolisation. Our results indicate that previous open surgery significantly predicted the occurrence of these lesions.
Aortic arch surgery in octogenarians: is it justified?

OBJECTIVES Elderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients. METHODS A total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan-Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey. RESULTS The patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group. CONCLUSIONS Surgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.
On wideband MIMO radar: Extended signal model and spectral beampattern design

MIMO radar systems can increase the radar resolution, the number of targets that can be identified, and the flexibility in beampattern design in comparison with standard phased array radars. To date, most of the work on MIMO radar has been performed assuming the signals are narrowband. However, wideband signals can improve radar resolution, among other benefits, and are sometimes unavoidable when stringent range resolution specifications must be met. In this paper, we present a method for extending the MIMO narrowband model to a wideband model. Next, from the exact expression of the spatial power distribution involving the CSDM (Cross-Spectral power Density Matrix), we propose a suboptimal transmit beampattern synthesis technique, which can be used in the context of wideband signals.
Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.

BACKGROUND Sarcopenia has been attributed to a diminished muscle protein synthetic response to food intake. Differences in digestion and absorption kinetics of dietary protein, its amino acid composition, or both have been suggested to modulate postprandial muscle protein accretion. OBJECTIVE The objective was to compare protein digestion and absorption kinetics and subsequent postprandial muscle protein accretion after ingestion of whey, casein, and casein hydrolysate in healthy older adults. DESIGN A total of 48 older men aged 74 ± 1 y (mean ± SEM) were randomly assigned to ingest a meal-like amount (20 g) of intrinsically l-[1-(13)C]phenylalanine-labeled whey, casein, or casein hydrolysate. Protein ingestion was combined with continuous intravenous l-[ring-(2)H(5)]phenylalanine infusion to assess in vivo digestion and absorption kinetics of dietary protein. Postprandial mixed muscle protein fractional synthetic rates (FSRs) were calculated from the ingested tracer. RESULTS The peak appearance rate of dietary protein-derived phenylalanine in the circulation was greater with whey and casein hydrolysate than with casein (P < 0.05). FSR values were higher after whey (0.15 ± 0.02%/h) than after casein (0.08 ± 0.01%/h; P < 0.01) and casein hydrolysate (0.10 ± 0.01%/h; P < 0.05) ingestion. A strong positive correlation (r = 0.66, P < 0.01) was observed between peak plasma leucine concentrations and postprandial FSR values. CONCLUSIONS Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. This effect is attributed to a combination of whey's faster digestion and absorption kinetics and higher leucine content. This trial was registered at clinicaltrials.gov as NCT00557388.
CCR5-Dependent Homing of T Regulatory Cells to the Tumor Microenvironment Contributes to Skin Squamous Cell Carcinoma Development

Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5- and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25−CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment. Mol Cancer Ther; 16(12); 2871–80. ©2017 AACR.
Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide.

PURPOSE We examined a consecutive series of 78 patients with non-Hodgkin's lymphoma treated on prospective protocols with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) plus autotransplantation to determine prognostic factors for time to treatment failure. PATIENTS AND METHODS Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support. Patient characteristics before transplantation were examined in univariate analyses by the log-rank test and simultaneously in a Cox proportional hazards regression analysis. A best-predictive model was determined from those variables significant (P < .10) in the univariate test. RESULTS In univariate analysis, intermediate-grade and immunoblastic lymphoma, responsiveness to pretransplant salvage chemotherapy, and transplantation after primary therapy (first complete response [CR] or partial response [PR]) were associated with prolonged time to treatment failure. In proportional hazards multiple regression analysis, intermediate-grade and immunoblastic histology, responsive disease, and autotransplantation in first CR or PR were positive prognostic factors, and these characteristics are the basis of the best-predictive model for prolonged time to failure. Actuarial 3-year failure-free survival of patients with stable or responding disease at autotransplant was 54%. CONCLUSION CBV is an effective conditioning regimen in intermediate-grade and immunoblastic non-Hodgkin's lymphoma. Patients with these histologies transplanted while responding to primary therapy, or those with stable disease or disease responding to salvage therapy at the time of autotransplant, are most likely to benefit. Patients with lymphoblastic lymphoma or diffuse undifferentiated lymphoma did poorly with CBV and should be offered alternative therapy.
Damaging diagnosis of myalgic encephalitis in children.

SIR,-We are being referred, from consultants and family doctors, a small but nevertheless worrying number of children and very young teenagers in whom a diagnosis of myalgic encephalitis has been made or suggested-in some cases because the mother has been diagnosed as having myalgic encephalitis. Some of these young subjects have received management and treatment which has not been put to the generally accepted tests of clinical efficacy or safety. Virtually all have had their quality of life further and seriously impaired by the application ofthe myalgic encephalitis label. The consequences have been serious with withdrawal from school, loss of contact with social peers, somatising of psychological problems, and lack of rational medical treatment, whether it be from a paediatrician or child psychiatrist. In most cases the diagnoses have been made or offered by parents with harassed practitioners acquiescing in the diagnosis without making the necessary rigorous clinical appraisal. In other cases the proffered diagnosis has led to extensive and unnecessary investigation. We believe that there is a more responsible role to be played by the ME Society. It should reconsider carefully whether it should encourage parents to consult doctors sympathetic to the diagnosis ofmyalgic encephalitis in adults, who are not necessarily best equipped to diagnose and manage these young patients. We have exercised forebearance by writing in these restrained terms, but we are concerned that a diagnosis of myalgic encephalitis may seriously damage a child's health. FRANK HARRIS
Network coding to enhance standard routing protocols in wireless mesh networks

This paper introduces a design and simulation of a locally optimized network coding protocol, called PlayNCool, for wireless mesh networks. PlayN-Cool is easy to implement and compatible with existing routing protocols and devices. This allows the system to gain from network coding capabilities implemented in software without the need for new hardware. PlayNCool enhances performance by (i) choosing a local helper between nodes in the path to strengthen the quality of each link, (ii) using local information to decide when and how many transmissions to allow from the helper, and (iii) using random linear network coding to increase the usefulness of each transmission from the helpers. This paper focuses on the design details needed to make the system operate in reality and evaluating performance using ns-3 in multi-hop topologies. Our results show that the PlayNCool protocol increases the end-to-end throughput by more than two-fold and up to four-fold in our settings.
Ibopamine challenge test can be used to differentiate glaucoma suspects from glaucoma patients

Many countries face the challenge of a rising number of patients with or at risk of developing glaucoma. A test to differentiate between people who are unlikely to develop glaucoma and those at risk for the disease could be clinically useful. Ibopamine, when administered topically, temporarily increases aqueous production. Normal eyes with healthy trabecular meshwork show no significant change in intraocular pressure (IOP) following an ibopamine challenge; however, those with glaucoma demonstrate elevated IOP.
Early trans-tibial oedema control using polymer gel socks

The aim of this investigation was to determine if early trans-tibial oedema control, by polymer gel socks prior to the fitting of a shrinker, could enhance trans-tibial stump volume reduction. Sixteen (16) adults, following unilateral trans-tibial amputation, were randomly allocated into 2 groups and baseline volume measurements taken of their stumps. The control group followed the normal removable rigid dressing programme, while the experimental group wore a polymer gel sock in conjunction with the removable rigid dressing. When wound healing permitted fitting of a shrinker, use of the polymer sock was discontinued and a stump volume measurement was taken. The shrinker was worn for a minimum of 2 days before casting for a prosthesis and a final stump volume measurement taken. Volumes were measured by water filling casts taken of the stump and calculated as a percentage of the baseline volume and the rate of volume reduction calculated. Two t-tests for unequal variance (2-tail, α=0.05) were used to compare the rate of percentage volume reduction between the groups, for the trial period of baseline to shrinker fitting and baseline to casting. A statistical difference was observed for the period of baseline to shrinker exceeding the 95% confidence limit (p<0.05). No significant difference was detected for the overall period of baseline to cast. It was concluded that early oedema control by polymer gel sock could enhance stump volume reduction, prior to a shrinker. It was also found that no volume advantage was carried over to the time of casting for a prosthesis.
Macroeconomic Eects of FOMC Forward Guidance

A large output gap accompanied by stable ination close to its target calls for further monetary accommodation, but the zero lower bound on interest rates has robbed the FOMC of the usual tool for its provision. This paper examines how public statements of FOMC intentions { forward guidance { can substitute for lower interest rates at the zero lower bound. We distinguish between Odyssean forward guidance, which publicly commits the FOMC to a future action, and Delphic forward guidance which merely forecasts future macroeconomic performance and likely monetary policy actions. Eggertsson and Woodford (2003) show how Odyssean forward guidance that commits to keep rates at zero for longer than conditions would otherwise warrant can provide monetary easing presently if the public trusts it. We empirically characterize the responses of asset prices and private macroeconomic forecasts to FOMC forward guidance, both before and since the recent nancial crisis. Our results show that the FOMC has extensive experience successfully telegraphing its intended adjustments to evolving macroeconomic conditions, so communications diculties do not present an insurmountable barrier to monetary policy based on Odyssean forward guidance. Using an estimated DSGE model, we then investigate how pairing Odyssean forward guidance with \bright-line" rules for launching rate increases can mitigate risks to the Federal Reserve’s price stability mandate.