Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Activation of Signal Transduction Pathways in Human Hearts With Hypertrophy Versus Advanced Heart Failure

Background —Left ventricular failure is commonly preceded by a period of hypertrophy. Intriguingly, many of the signaling pathways that have been implicated in the regulation of hypertrophy, including the 3 mitogen-activated protein kinases (MAPKs: extracellular signal-regulated kinase, stress-activated protein kinase, and p38), protein phosphatase, calcineurin, and the protein kinase Akt and its target glycogen synthase kinase-3 (GSK-3), also regulate the apoptotic response. Methods and Results —To understand the mechanisms that might regulate the progression of heart failure, we analyzed the activity of these signaling pathways in the hearts of patients with advanced heart failure, patients with compensated cardiac hypertrophy, and normal subjects. In patients with hypertrophy, neither the MAPK nor the Akt/GSK-3 pathways were activated, and the dominant signaling pathway was calcineurin. In failing hearts, calcineurin activity was increased but less so than in the hypertrophied hearts, and all 3 MAPKs and Akt were activated (and, accordingly, GSK-3&bgr; was inhibited), irrespective of whether the underlying diagnosis was ischemic or idiopathic cardiomyopathy. Conclusions —In the failing heart, there is a clear prohypertrophic activity profile, likely occurring in response to increased systolic wall stress and neurohormonal mediators. However, with the activation of these hypertrophic pathways, potent proapoptotic and antiapoptotic signals may also be generated. Therapies directed at altering the balance of activity of these signaling pathways could potentially alter the progression of heart failure.
Rural Hospital Web-Based, Evidence-Based Practice Professional Development: Challenges and Opportunities

To provide quality patient care and achieve positive patient outcomes, it is widely recognized that organizations must develop a supportive environment that encourages individuals to practice from a research- and evidence-based framework. This article describes a Web-based professional educational program designed to teach principles of evidence-based practice to nurses in rural hospitals. Nurses working in staff development will find this useful for designing educational programs for staff in rural hospitals.
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency

The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and α-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the α-granule content by immunofluorescence analysis for α-granule secretory proteins. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet α-granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the α-granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the α-granule deficiency than individuals with two NBEAL2 mutated alleles. Our data extend the spectrum of mutations responsible for gray platelet syndrome and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype.
Fear of Pain Questionnaire‐9: Brief assessment of pain‐related fear and anxiety

Fear and anxiety are important considerations in both acute and chronic pain. Effectively and efficiently measuring fear and anxiety associated with pain in healthcare settings is critical for identifying vulnerable patients. The length and administration time of current measures of pain‐related fear and anxiety inhibit their routine use, as screening tools and otherwise, suggesting the need for a shorter, more efficient instrument.
The relationship between foveal ischemia and spectral-domain optical coherence tomography findings in ischemic diabetic macular edema.

PURPOSE To investigate the relationship between enlargement of the foveal avascular zone (FAZ) and structural changes on spectral-domain optical coherence tomography (SD-OCT) in patients with ischemic diabetic macular edema (DME). METHODS This was a retrospective, cross-sectional study including 35 eyes of 33 patients with ischemic DME as determined by irregular margins of the FAZ in fluorescein angiography. We measured the best-corrected visual acuity (BCVA), central subfield thickness (CST), subfield volume, subfoveal choroidal thickness, length of the photoreceptor outer segment (PR-OS), and the lateral extent of inner segment-outer segment (IS-OS) disruption on SD-OCT images, as well as the FAZ to optic nerve head (FAZ/ONH) area ratio by using the ImageJ program. RESULTS The mean FAZ/ONH area ratio was 0.28 ± 0.15. The FAZ/ONH area ratio was positively correlated with the logarithm of the minimum angle of resolution (LogMAR) BCVA (P = 0.001, r = 0.529). The mean CST was 391 ± 110 μm, and the subfield volume was 0.31 ± 0.09 mm(3). The mean length of the PR-OS and the horizontal and vertical extent of IS-OS disruption were 40 ± 8 μm, 169 ± 294 μm, and 114 ± 170 μm, respectively. The mean length of the PR-OS and the horizontal and vertical extent of IS-OS disruption were significantly correlated with FAZ/ONH area ratio (P = 0.020, P = 0.001, and P = 0.049, respectively). The horizontal and vertical extent of IS-OS disruption showed a positive correlation with LogMAR BCVA (P = 0.027 and P = 0.049, respectively). CONCLUSIONS Foveal ischemia in DME appears to cause PR-OS shortening and IS-OS disruption resulting in outer retinal layer atrophic changes and subsequent visual loss.
Functional Genomic Studies of the Intestinal Response to a Foodborne Enteropathogen in a Humanized Gnotobiotic Mouse Model*

Members of the genus Listeria provide a model for defining host responses to invasive foodborne enteropathogens. Active translocation of Listeria monocytogenes across the gut epithelial barrier is mediated by interaction of bacterial internalin (InlA) and its species-specific host receptor, E-cadherin, whereas translocation across Peyer's patches through M-cells is InlA-independent. To define microbial determinants and molecular correlates of the host response to translocation via these two routes, we colonized germ-free transgenic mice expressing the human enterocyte-associated E-cadherin receptor with wild-type (WT) or mutant L. monocytogenes strains, or its nonpathogenic noninvasive relative Listeria innocua, or with Bacteroides thetaiotaomicron, a prominent gut symbiont. Mouse Gene-Chips, combined with Ingenuity Pathway software, were used to identify canonical signaling pathways that comprise the response to WT L. monocytogenes versus the other species. Gain- and loss-of-function experiments with L. innocua and L. monocytogenes, respectively, demonstrated that the 773-member transcriptional signature of the response to WT L. monocytogenes is largely conserved in the ΔinlA mutant. Internalin-dependent responses include down-regulation of gene networks involved in various aspects of lipid, amino acid, and energy metabolism and up-regulation of immunoinflammatory responses. The host response is markedly attenuated in a listeriolysin-deficient (Δhly) mutant despite its ability to be translocated to the lamina propria. Together, these studies establish that hly, rather than bacterial invasion of the lamina propria mediated by InlA, is a dominant determinant of the intensity of the host response to L. monocytogenes infection via the oral route.
Advection-Dominated Accretion and the Spectral States of Black Hole X-Ray Binaries: Application to Nova Muscae 1991

Black hole X-ray binaries (BHXBs) are known to display five distinct spectral states. In order of increasing luminosity these are the quiescent state, low state, intermediate state, high state, and very high state. We present a self-consistent model of accretion flows around black holes that unifies all of these states except the very high state. The model is an extension of the following paradigm, which has been applied successfully to the quiescent state. The accretion flow consists of two zones, an inner advection-dominated accretion flow (ADAF) that extends from the black hole horizon to a transition radius rtr, and an outer thin accretion disk that is present beyond rtr. Above the disk is a hot corona, which is a continuation of the inner ADAF. The model consistently treats the dynamics of the accreting gas, the thermal balance of the ions and electrons in the two-temperature ADAF and corona, and the radiation processes that produce the observed spectrum. At low mass accretion rates, ṁ ≲ 0.01 (in Eddington units), the inner ADAF zone in the model radiates extremely inefficiently, and the outer thin disk is restricted to large radii (rtr ~ 102-104, in Schwarzschild units). The luminosity therefore is low, and this configuration is identified with the quiescent state. For ṁ ≳ 0.01 and up to a critical value ṁcrit ~0.08, the radiative efficiency of the ADAF increases rapidly and the system becomes fairly luminous. The spectrum is very hard and peaks around 100 keV. This is the low state. The exact value of ṁcrit depends on the viscosity parameter α (ṁcrit ~1.3α2; the paper assumes α = 0.25). For values of ṁ > ṁcrit and up to a second critical value about 10% higher, the ADAF progressively shrinks in size, the transition radius decreases, and the X-ray spectrum changes continuously from hard to soft. We identify this stage with the intermediate state. Finally, when ṁ is sufficiently large, the inner ADAF zone disappears altogether and the thin accretion disk extends down to the marginally stable orbit. The spectrum is dominated by an ultrasoft component with a weak hard tail. This is the high state. Model spectra calculated with this unified scenario agree well with observations of the quiescent, low, intermediate, and high states. Moreover, the model provides a natural explanation for the low state to high state transition in BHXBs. We also make a tentative proposal for the very high state, but this aspect of the model is less secure. An important feature of the model is that it is essentially parameter free. We test the model against observations of the soft X-ray transient Nova Muscae during its 1991 outburst. The model reproduces the observed light curves and spectra surprisingly well and makes a number of predictions that can be tested by observations of other BHXBs.
Advances in Powder Metallurgy: Properties, Processing and Applications

Part 1 Forming and shaping of metal powders: Advances in atomisation techniques for the formation of metal powders Forming metal powders by electrolysis Mechanochemical synthesis of nanocrystalline metal powders Plasma synthesis of metallic nanopowders Warm compaction of metallic powders Developments in metal injection moulding (MIM). Part 2 Materials and properties: Advanced powder metallurgy steel alloys Powder metallurgy of titanium alloys Metal-based composite powders Porous metals: Foams and sponges Evolution of microstructure in ferrous and non-ferrous powdered metals. Part 3 Manufacturing and densification of PM components: Microwave sintering of metal powders Joining techniques for powder metallurgy components Process optimisation in powder component manufacturing Non-destructive evaluation of powder metallurgy parts Fatigue and fracture of powder metallurgy steels. Part 4 Applications: Automotive applications of powder metallurgy Applications of powder metallurgy in biomaterials Applications of powder metallurgy in cutting tools.
Robust microcapsules with polyurea/silica hybrid shell for one-part self-healing anticorrosion coatings

Silica/polyurea hybrid microcapsules loaded with hexamethylene diisocyanate (HDI) as core materials were prepared via a combined strategy of interfacial polymerization and an in situ sol–gel process in an oil-in-water emulsion. They were clearly characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The resultant microcapsules have diameters of 57–328 μm, shell thicknesses of 1–8 μm, and core fractions of 51.2–65.6%. The diameter and shell thickness were linearly related to the agitation rate in the double logarithm coordinates, and the core fraction were linearly related to the agitation rate, indicating that the structure and component of the microcapsules can be controlled effectively. The resistant properties against thermal and solvent attacks were assessed by using thermogravimetric analysis and titration. The results show that the microcapsules had outstanding thermal stability with initial evaporation temperature (defined at 5% of weight loss), increased by around 58 °C compared with that of pure core material, and good resistance to xylene with less than 25.9 ± 0.7 wt% reduction of core content after immersion for 100 h. Self-healing anticorrosion coatings based on microcapsules were fabricated on a steel substrate. Preliminary results indicated significant corrosion retardancy occurred in the coatings under an accelerated corrosion process, showing the great potential of our microcapsules in the development of catalyst-free, one-part, self-healing coatings for corrosion control.
Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila

Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line‐cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient‐poor larval food for 84 generations. We assayed three fitness‐related traits (developmental rate, adult female weight and egg‐to‐adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.
Cone-beam computed tomographic analysis of sinus membrane thickness, ostium patency, and residual ridge heights in the posterior maxilla: implications for sinus floor elevation.

OBJECTIVE To determine, using cone-beam computed tomography (CBCT), the residual ridge height (RRH), sinus floor membrane thickness (MT), and ostium patency (OP) in patients being evaluated for implant placement in the posterior maxilla. MATERIALS AND METHODS CBCT scans of 128 patients (199 sinuses) with ≥1 missing teeth in the posterior maxilla were examined. RRH and MT corresponding to each edentulous site were measured. MT >2 mm was considered pathological and categorized by degree of thickening (2-5, 5-10 mm, and >10 mm). Mucosal appearance was classified as "normal", "flat thickening", or "polypoid thickening", and OP was classified as "patent" or "obstructed". Descriptive and bivariate statistical analyses were performed. RESULTS MT >2 mm was observed in 60.6% patients and 53.6% sinuses. Flat and polypoid mucosal thickening had a prevalence of 38.1% and 15.5%, respectively. RRH ≤4 mm was observed in 46.9% and 48.9% of edentulous first and second molar sites, respectively. Ostium obstruction was observed in 13.1% sinuses and was associated with MT of 2-5 mm (6.7%), 5-10 mm (24%), and >10 mm (35.3%, P < 0.001). Polypoid mucosal lesions were more frequently associated with ostium obstruction than flat thickenings (26.7% vs. 17.6%, P < 0.001). CONCLUSION Thickened sinus membranes (>2 mm) and reduced residual ridge heights (≤4 mm) were highly prevalent in this sample of patients with missing posterior maxillary teeth. Membrane thickening >5 mm, especially of a polypoid type, is associated with an increased risk for ostium obstruction. In the presence of these findings, an ENT referral may be beneficial prior to implant-related sinus floor elevation.
The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma

Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. Results: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9–27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6–30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2–21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. Conclusions: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.
Oligomerization of the Na,K-ATPase in Cell Membranes*

The higher order oligomeric state of the Na,K-ATPase αβ heterodimer in cell membranes is the subject of controversy. We have utilized the baculovirus-infected insect cell system to express Na,K-ATPase with α-subunits bearing either His6 or FLAG epitopes at the carboxyl terminus. Each of these constructs produced functional Na,K-ATPase αβ heterodimers that were delivered to the plasma membrane (PM). Cells were simultaneously co-infected with viruses encoding α-His/β and α-FLAG/β Na,K-ATPases. Co-immunoprecipitation of the His-tagged α-subunit in the endoplasmic reticulum (ER) and PM fractions of co-infected cells by the anti-FLAG antibody demonstrates that protein-protein associations exist between these heterodimers. This suggests the Na,K-ATPase is present in cell membranes in an oligomeric state of at least (αβ)2 composition. Deletion of 256 amino acid residues from the central cytoplasmic loop of the α-subunit results in the deletion α-4,5-loop-less (α-4,5LL), which associates with β but is confined to the ER. Co-immunoprecipitation demonstrates that when this inactive α-4,5LL/β heterodimer is co-expressed with wild-type αβ, oligomers of wild-type αβ and α-4,5LL/β form in the ER, but the α-4,5LL mutant remains retained in the ER, and the wild-type protein is still delivered to the PM. We conclude that the Na,K-ATPase is present as oligomers of the monomeric αβ heterodimer in native cell membranes.
Identifying Priorities for Emergency Intervention from Child Wasting and Mortality Estimates in Vulnerable Areas of the Horn of Africa

Background The relation between anthropometric measures and mortality risk in different populations can provide a basis for deciding how malnutrition prevalences should be interpreted. Objective To assess criteria for deciding on needs for emergency interventions in the Horn of Africa based on associations between child wasting and mortality from 2000 to 2005. Methods Data were analyzed on child global acute malnutrition (GAM) prevalences and mortality estimates from about 900 area-level nutrition surveys from Ethiopia, Kenya, Somalia, Sudan, and Uganda; data on drought, floods, and food insecurity were added for Kenya (Rift Valley) and Ethiopia, from Food and Agriculture Organization (FAO) reports at the time. Results Higher rates of GAM were associated with increased mortality of children under 5 years of age (U5MR), more strongly among populations with pastoral livelihoods than with agricultural livelihoods. In all groups spikes of GAM and U5MR corresponded with drought (and floods). Different GAM cutoff points are needed for different populations. For example, to identify 75% of U5MRs above 2/10,000/day, the GAM cutoff point ranged from 20% GAM in the Rift Valley (Kenya) to 8% in Oromia or SNNPR (Ethiopia). Conclusions Survey results should be displayed as time series within geographic areas. Variable GAM cutoff points should be used, depending on livelihood or location. For example, a GAM cutoff point of 15% may be appropriate for pastoral groups and 10% for agricultural livelihood groups. This gives a basis for reexamining the guidelines currently used for interpreting wasting (or GAM) prevalences in terms of implications for intervention.
Late onset of primary pulmonary primitive neuroectodermal tumor: a case report

Lungs are one of most metastatic areas for primitive neuroectodermal tumor (PNET), however primary pulmonary PNET is extremely rare. Here we present a case of a 58-year-old male patient with a tumor in the right lung that originated from the lung but not from chest wall. Patient was diagnosed with PNET following histological and immunohistochemical examination of CT-guided percutaneous tru-cut needle biopsy and no distant metastasis were detected in PET-CT scan. As advised recently in published literature, surgical resection following neoadjuvant chemotherapy protocol is preferred in the treatment of our patient as it has better success of complete resection leading to higher 5-year survival rates. Although primary pulmonary PNET is uncommon, it should be taken into account and complete surgical resection should be aimed as treatment to achieve higher survival rates.