Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of valve prosthesis–patient mismatch prior to aortic valve replacement: which is the best method?

Background: To predict the occurrence of valve prosthesis–patient mismatch (VP–PM) after aortic valve replacement (AVR), the surgeon needs to estimate the postoperative effective orifice area index (EOAI). Aim: To compare different methods of predicting VP–PM. Methods: The effective orifice area (EOA) of 383 patients who had undergone AVR between July 2000 and January 2005 with various aortic valve prostheses was obtained echocardiographically 6 months after the operation. We tested the efficacy of (1) EOAI calculated from the echo data obtained in our own laboratory, (2) indexed geometric orifice area, (3) EOAI estimated from charts provided by prosthesis manufacturers (which are based either on in vitro or on echo data) and (4) EOAI estimated from reference echo data published in the literature to predict VP–PM. Results: Sensitivity and specificity to predict VP–PM were 53% and 83% (method 1), 80% and 53% (charts based on echo data, parts of method 3) and 71% and 67% (method 4) using reference data derived from echocardiographic examinations. The sensitivity of method 2 and of charts based on in vitro data (parts of method 3) to predict VP–PM was 0–17%. The incidence of severe VP–PM could be reduced from 8.7% to 0.8% after the introduction of the systematic estimation of the EOAI at the time of operation (p = 0.003, method 1). Conclusions: The best method of predicting VP–PM is the use of mean (SD) EOAs derived from echocardiographic examinations, whereas the use of in vitro data or the geometric orifice area is unreliable. After the surgeon’s anticipation of VP–PM prior to AVR, the incidence of VP–PM could be reduced.
Hepatic MR Elastography: Clinical Performance in a Series of 1377 Consecutive Examinations.

PURPOSE To assess the technical success rate and diagnostic performance of liver magnetic resonance (MR) elastography. MATERIALS AND METHODS This retrospective study was approved by the institutional review board with patient informed consent. A total of 1377 consecutive MR elastography examinations performed between 2007 and 2010 in 1287 patients for clinical indications were included. Medical records were used to retrieve liver stiffness as assessed with MR elastography, histologic analysis, blood work, and other liver disease-related information. Nonparametric Kruskal-Wallis tests and analysis of covariance methods were used to evaluate the diagnostic values and relationships of the collected data. RESULTS Hepatic MR elastography had a success rate of 94.4% (1300 of 1377 cases) and yielded reproducible measurements (r = 0.9716, P < .0001) in the study cohort, with a complex patient profile and multiple interpreters. Body mass index had no significant effect on success rate (P = .2). In 289 patients who underwent liver biopsy within 1 year of the MR elastography date, mean liver stiffness as assessed with MR elastography was significantly higher in patients with advanced fibrosis (stages F3, F4) than in those with mild to moderate fibrosis (stages F0, F1, F2) (5.93 kPa ± 2.31 [standard deviation] vs 3.35 kPa ± 1.44, P < .0001). Liver stiffness is associated with many factors other than fibrosis extent, including cause of fibrosis (viral hepatitis C vs nonalcoholic fatty liver disease, P = .025), inflammation (severe vs mild to moderate, P = .03), and hepatic metabolic and synthetic function (no fibrosis vs intermediate fibrosis, P ≤ .01). CONCLUSION In a general clinical practice environment, hepatic MR elastography is a robust imaging method with a high success rate in a broad spectrum of patients. It also shows the complex association between liver stiffness and hepatic pathophysiology.
Muscle and fat metabolism in obesity after kidney transplantation: no effect of peritoneal dialysis or hemodialysis.

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 μg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 μmol/L; P < . 01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < . 01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.
Activin and Follicle-Stimulating Hormone Signaling Are Required for Long-Term Culture of Functionally Differentiated Primary Granulosa Cells from the Chicken Ovary1

Abstract Follicle-stimulating hormone, activin A, and transforming growth factor (TGF) α are important regulators of chicken granulosa cell (cGC) function. Hence, we aimed to test whether these growth factors are useful for establishing a suitable in vitro cell culture model system of primary cGC. Although cGC are easily isolated from distinct follicular stages, a long-term cGC culture system for in vitro studies has been unavailable. Here, we report a novel, long-term cell culture system that allows for cGC proliferation in vitro while maintaining the epithelial phenotype that granulosa cells exhibit in vivo. The cGC rapidly lose their epithelial morphology and acquire a mesenchymal or fibroblastoid phenotype when cultured in the absence of activin A. This process is strongly enhanced by TGFα, a well-known granulosa cell mitogen. However, FSH stimulates cGC proliferation without enhancing morphological changes and dedifferentiation. Interestingly, a combination of both activin A and FSH stimulates cGC proliferation and supports maintenance of differentiated epithelial morphology. Furthermore, activin A and FSH synergistically induce granulosa cell-specific differentiation markers such as inhibin α and chicken zona pellucida protein C, suggesting that cultured cGC resemble functionally differentiated granulosa cells. Our data demonstrate that activin signaling is necessary to sustain a morphologically differentiated phenotype of cGC in vitro. The results also suggest a pivotal importance of activin signaling for granulosa cell function in vivo.
IgE and non-IgE-mediated food allergy: treatment in 2007

Purpose of review Our understanding of the mechanism of food allergy has substantially increased over the past decade. Food allergies can be classified into those that are IgE mediated and those that are non-IgE mediated. Recent findings Various advances have been made in treating IgE-mediated food allergies. A phase II clinical trial of a second anti-IgE antibody, omalizumab, was recently initiated in subjects with peanut allergy, but was stopped as a result of safety concerns after severe reactions occurred during initial oral challenges. Oral immunotherapy is showing promise in various studies on patients with IgE-mediated food allergies. Gastrointestinal food allergic disorders involving non-IgE-mediated food allergies have recently received attention, particularly eosinophilic esophagitis. Although amino acid-based formula therapy remains the most successful in controlling inflammation and symptoms in these disorders, other therapeutic options including various dietary elimination protocols and swallowed fluticasone are showing success. Anti-IL-5 therapy may prove to be a promising future therapeutic option for refractory patients. Summary Although there are no specific therapeutic recommendations for many IgE-mediated and non-IgE-mediated food allergic disorders besides allergen avoidance, various novel approaches are currently being investigated and may influence treatment approaches in the future.
A Novel Approach to Regulate Experimental Visceral Leishmaniasis in Murine Macrophages using CCR5 siRNA

Early infection with Leishmania donovani during visceral leishmaniasis (VL) results in the enhanced expression of C‐C chemokine receptor 5 (CCR5) in macrophages. CCR5 expression at different time points of infection revealed increased expression at protein and mRNA level from 3 to 24 h and beyond 24 h expression of CCR5 is downregulated. To better understand the functional role of CCR5 during leishmania infection, RNA interference strategy has been used to modulate macrophage function by targeting the expression of CCR5 gene. We found that silencing of CCR5 receptor expression by transfection of CCR5‐specific small interfering RNA (siRNA) in murine peritoneal macrophages restricted the parasitic burden up to 70% during early hours of infection. In addition, gene silencing of CCR5 prior to L. donovani infection enhanced the pro‐inflammatory response of the host macrophages in comparison with infection alone as shown by high nitric oxide generation and the TNF‐α:IL‐10 ratio. These findings suggest that CCR5 receptor plays a significant role in the entry and establishment of L. donovani in murine macrophages and CCR5 gene silencing would be a potent therapeutic approach to control VL by restricting parasite entry.
Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule.

BACKGROUND The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R-EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here. METHODS We performed a MEDLINE search using “bronchoscopy” and “solitary pulmonary nodule. ” Studies evaluating the diagnostic yield of ENB, VB, R-EBUS, ultrathin bronchoscope, and/or guide sheath for peripheral nodules were included. The overall diagnostic yield and yield based on size were extracted. Adverse events, if reported, were recorded. Meta-analysis techniques incorporating inverse variance weighting and a random-effects meta-analysis approach were used. RESULTS A total of 3,052 lesions from 39 studies were included. The pooled diagnostic yield was 70%, which is higher than the yield for traditional transbronchial biopsy. The yield increased as the lesion size increased. The pneumothorax rate was 1.5%, which is significantly smaller than that reported for TTNA. CONCLUSION This meta-analysis shows that the diagnostic yield of guided bronchoscopic techniques is better than that of traditional transbronchial biopsy. Although the yield remains lower than that of TTNA, the procedural risk is lower. Guided bronchoscopy may be an alternative or be complementary to TTNA for tissue sampling of PN, but further study is needed to determine its role in the evaluation of peripheral pulmonary lesions.
Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation

Vascular endothelial cell (VEC) proliferation is a key event in angiogenesis and is tightly regulated. Electric potential differences exist around the vascular endothelium and give rise to endogenous electric fields (EFs), whether these EFs influence VEC proliferation is unclear. We exposed cultured VECs to applied EFs of physiological strengths for up to 72 h. EF at 50 or 100 mV/mm did not influence cell proliferation, but at 200 mV/mm, cell density, cell growth rate, and mitosis index decreased significantly. EF‐induced reduction in VEC proliferation was not due to increased apoptosis, because caspase apoptosis inhibitor Z‐VAD‐FMK (20 μM), had no effect on this response. Rather, EF responses were mediated via decreased entry of cells into S phase from G1 phase, as shown by flow cytometry. Western blot showed that EFs decreased G1‐specific cyclin E expression and increased cyclin/cyclin‐dependent kinase complex inhibitor p27kip1 expression. Thus EFs controlled VEC proliferation through induction of cell cycle arrest at G1 by down‐regulation of cyclin E expression and up‐regulation of p27kip1expression, rather than by promoting apoptosis. If control of the cell cycle by endogenous EFs extends beyond VECs, this would be of widespread biological significance in vivo.
Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor‐KappaB Signaling

Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high‐resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue‐simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor‐kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue‐related diseases. Stem Cells 2016;34:601–613
Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98.

PURPOSE To evaluate locally versus centrally assessed estrogen (ER) and progesterone (PgR) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer. PATIENTS AND METHODS Breast International Group (BIG) 1-98 randomly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent. The Central Pathology Office received material for 6,549 patients (82%), of which 79% were assessable (6,291 patients). Prognostic and predictive value of both local and central hormone receptor expression on disease-free survival (DFS) were evaluated among 3,650 assessable patients assigned to the monotherapy arms. Prognostic value and the treatment effect were estimated for centrally assessed ER and PgR expression levels using the Subpopulation Treatment Effect Pattern Plot. RESULTS Central review confirmed 97% of tumors as hormone receptor-positive (ER and/or PgR > or =10%). Of 105 tumors locally ER-negative, 73 were found to have more than 10% positive cells, and eight had 1% to 9%. Of 6,100 tumors locally ER positive, 66 were found to have no staining, and 54 had only 1% to 9%. Discordance was more marked for PgR than ER. Patients with tumors reclassified centrally as ER-negative, or as hormone receptor-negative, had poor DFS. Centrally assessed ER and PgR showed prognostic value. Among patients with centrally assessed ER-expressing tumors, letrozole showed better DFS than tamoxifen, irrespective of PgR expression level. CONCLUSION Central review changed the assessment of receptor status in a substantial proportion of patients, and should be performed whenever possible in similar trials. PgR expression did not affect the relative efficacy of letrozole over tamoxifen.
Survival of multiple sclerosis in Finland between 1964 and 1993

The long-term survival of multiple sclerosis (MS) was studied during 1964-1993 in a cohort of 1614 patients in Finland. Survival to death from the initial MS symptoms was analysed by the life-table method, separately for MS related and all causes of deaths. Survival at 40 years was 64% for MS deaths and 53% for all deaths. Higher proportions of violent deaths and neoplasms were observed among MS patients as compared to the general population, whereas the proportion of cardiovascular causes of death was low. MS-related causes accounted for 70% of the recorded 219 deaths. Favourable survival in MS was associated with relapsing-remitting disease course, age at onset below 30 years and optic neuritis or other sensory symptoms at presentation. We were unable to show any significant effect due to calendar time of diagnosis or gender, as the risk of men was similar (risk ratio [RR]=1.1, confidence interval [CI] 0.8-1.6) as compared to women.
Mapping retinal degeneration and loss-of-function in Rd-FTL mice.

PURPOSE Retinitis pigmentosa (RP) is a blinding disease caused by the degeneration of photoreceptors. To further understand the process of degeneration in RP, the authors have traced activation patterns associated with rod and cone photoreceptor degeneration in a mouse model of RP METHODS: The authors used a double-mutant mouse, Rd-FTL, which contains a natural mutation, rd1, affecting the rod photoreceptors and an axon-targeted beta-galactosidase reporter system, which is under the regulation of the promoter of the c-fos gene. These mice allowed the authors to trace degeneration-related activity that corresponded to rod and cone death. RESULTS The authors traced cell death-associated activation in both rods and cones, allowing them to accurately determine the time course of cone degeneration in these mice. In the analysis of downstream activation patterns in the inner retina, they found that amacrine and ganglion cells maintain their photopic light-related activation until at least the initiation of cone degeneration. These cell populations then show increased activity during the peak time of cone cell degeneration. The authors also examined light-regulated functional activation of a subclass of amacrine cells, the dopaminergic amacrine cells. These cells showed light-induced functional activation after rod photoreceptor death and until the period of cone photoreceptor death, suggesting that they can be regulated by cone photoreceptors alone. CONCLUSIONS These findings have helped to accurately trace the periods of photoreceptor degeneration in this model of RP and show that correct light-regulated inner retinal activation is maintained until the time of cone degeneration.
Ultra low contact resistivity (< 1×10−8 Ω-cm2) to In0.53Ga0.47As fin sidewall (110)/(100) surfaces: Realized with a VLSI processed III–V fin TLM structure fabricated with III–V on Si substrates

We report a record low contact resistivity of sub-1.0×10<sup>-8</sup> Ω. cm<sup>2</sup> realized on n<sup>+</sup> In<sub>0.53</sub>Ga<sub>0.47</sub>As fin sidewall surfaces. This is achieved with VLSI processed fin TLM structures on wafer scale III-V on Si substrates. A novel low-damage III-V fin etch was developed and fins down to 35 nm were fabricated. A surface treatment to smoothen the fin sidewall surfaces was proposed, which reduced sidewall surface roughness variation by 90%. Additionally, we show for the first time that implant temperature could be used to eliminate implant damage in III-V fins. This increased activation efficiency (+3.6×) and reduced sheet resistance (-60%).
Relationship between nickel and cobalt sensitization in hard metal workers

853 hard metal workers were examined and patch tested with 20 substances from their environment, including nickel and cobalt. Nickel sensitivity was found in 2 men and 38 women. 88% of the nickel‐sensitive individuals had developed a jewellery dermatitis prior to employment in the hard metal industry or before the appearance of hand eczema. 29% of the hard metal workers gave a history of slight irrifant dermatitis. In the nickel sensitized group, 40% had had severe hand eczema which generally appeared 6–12 months after starting employment. In 25% of the cases, nickel sensitive individuals developed cobalt allergy, compared with 5% in the total population investigated. Most facts indicate that nickel sensitivity and irritant hand eczema precede cobalt sensitization. Hard metal workers with simultaneous nickel and cobalt sensitivity had a more severe hand eczema than those with isolated cobalt or nickel sensitivity or only irritant dermatitis. 64% of the female population had pierced ear lobes. Among the nickel allergic women, 95% had pierced ear lobes. The use of earrings containing nickel after piercing is strongly suspected of being the major cause of nickel sensitivity. Piercing at an early age seems to increase the risk of incurring nickel sensitivity.
Predicting High Blood Metal Ion Concentrations following Hip Resurfacing

Purpose To determine whether gender, femoral head size, acetabular inclination, and time since surgery predicted high blood metal ion concentrations following Birmingham Hip Resurfacing (BHR). Methods BHR patients with unilateral bearings at one specialist centre with blood cobalt and chromium concentrations measured up to May 2013 were included. This comprised a mixed (at-risk) group including symptomatic patients and asymptomatic individuals with specific clinical and/or radiological findings. Blood sampling was at a mean of 7.5 years (range 1-15.4 years) postoperatively. Results Of 319 patients (mean age 49.3 years; 53% male), blood metal ions greater than 7 µg/l were observed in 9% (n = 28). Blood metal ions were significantly higher in females (p<0.001), femoral head sizes ≤48 mm (p<0.01), and cup inclinations >55° (p<0.001). Linear regression demonstrated femoral head size was responsible for the highest proportion of variance in blood metal ions (cobalt p<0.001, R2 = 8%; chromium p<0.001, R2 = 11%). Analysis of femoral head size and inclination together demonstrated 36% of BHRs with head sizes of 38-44 mm and inclination >55° had blood metal ions >7 µg/l. BHR 10-year survival for this at-risk group was 91% (95% confidence intervals 86.0%-95.0%) with 30 hips revised. Conclusions If blood metal ions are used to screen hip resurfacing patients for adverse reactions to metal debris it is recommended those with small femoral head sizes (38-44 mm) and high acetabular inclinations (>55°) are targeted. These findings require validation in other cohorts as they may not be applicable to all hip resurfacing devices given the differences in radial clearance, coverage arc, and metallurgy.