Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac resynchronization therapy in patients with end-stage hypertrophic cardiomyopathy

AIMS A dilated/end-stage phase of hypertrophic cardiomyopathy (HCM) is rare but well-recognized. The role for cardiac resynchronization therapy (CRT) in this subset of patients remains unexplored. We aimed to clarify the impact of bi-ventricular pacing CRT in dilated/end-stage HCM. METHODS AND RESULTS The Mayo Clinic HCM database was interrogated to identify patients with ejection fraction (EF) <50% and CRT. Control subjects were identified in 1:1 manner. Clinical outcomes were determined. Of 2073 patients with HCM, 9 (8 male) had EF <50% and received CRT. The average age at CRT-D implant was 44.8 ± 14.8 years, an average of 17.3 ± 10.3 years after HCM diagnosis. The indication for CRT was based on New York Heart Association class ≥II symptoms (mean 2.7 ± 0.4) and EF <50% in all patients (EF 34.7 ± 7.1% at implant), with electrocardiographic evidence of abnormal ventricular conduction. At 6-month, 12-month, and long-term follow-up, EF was 39.9 ± 8.4%, 37.9 ± 9.8%, and 33.3 ± 7.6%, respectively (P > 0.05 for all). There was no difference in the combined end-point of left ventricular assist device (LVAD), cardiac transplant, or death between groups (P = 0.90). At last follow-up [mean duration 12.9 ± 8.3 (median 10.7) years], 8 (89%) in the CRT group were alive. Three and 2 patients underwent LVAD implantation and cardiac heart transplantation, respectively, 15.0 ± 10.1 years from HCM diagnosis and 2.6 ± 0.9 years from CRT implant. In the control group, 4 (44.4%) patients were alive at last follow-up [mean duration 12.0 ± 7.1 (median 12.7) years]. One patient each had LVAD and cardiac transplant. CONCLUSIONS CRT in patients with dilated/end-stage HCM does not appear to confer a salutary effect on ventricular function. In medium-term follow-up, however, left ventricular function did not appear to deteriorate further, yet advanced heart failure therapy was common in this group.
New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection

Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells. While α-enolase is present in all neurological tissues, it can also be converted to neuron specific enolase (NSE). NSE is a glycolytic enzyme found in neuronal and neuroendocrine tissues that may play a dual role in promoting both neuroinflammation and neuroprotection in SCI and other neurodegenerative events. Elevated NSE can promote ECM degradation, inflammatory glial cell proliferation, and actin remodeling, thereby affecting migration of activated macrophages and microglia to the injury site and promoting neuronal cell death. Thus, NSE could be a reliable, quantitative, and specific marker of neuronal injury. Depending on the injury, disease, and microenvironment, NSE may also show neurotrophic function as it controls neuronal survival, differentiation, and neurite regeneration via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. This review discusses possible implications of NSE expression and activity in neuroinflammation, neurodegeneration, and neuroprotection in SCI and various neurodegenerative diseases for prognostic and therapeutic potential.
Microbial lipid extraction from Lipomyces starkeyi using irreversible electroporation

The aim of the study was to investigate the feasibility of using irreversible electroporation (EP) as a microbial cell disruption technique to extract intracellular lipid within short time and in an eco‐friendly manner. An EP circuit was designed and fabricated to obtain 4 kV with frequency of 100 Hz of square waves. The yeast cells of Lipomyces starkeyi (L. starkeyi) were treated by EP for 2‐10 min where the distance between electrodes was maintained at 2, 4, and 6 cm. Colony forming units (CFU) were counted to observe the cell viability under the high voltage electric field. The forces of the pulsing electric field caused significant damage to the cell wall of L. starkeyi and the disruption of microbial cells was visualized by field emission scanning electron microscopic (FESEM) image. After breaking the cell wall, lipid was extracted and measured to assess the efficiency of EP over other techniques. The extent of cell inactivation was up to 95% when the electrodes were placed at the distance of 2 cm, which provided high treatment intensity (36.7 kWh m−3). At this condition, maximum lipid (63 mg g−1) was extracted when the biomass was treated for 10 min. During the comparison, EP could extract 31.88% lipid while the amount was 11.89% for ultrasonic and 16.8% for Fenton's reagent. The results recommend that the EP is a promising technique for lowering the time and solvent usage for lipid extraction from microbial biomass. © 2018 American Institute of Chemical Engineers Biotechnol. Prog. , 34:838–845, 2018
A new approach to the production of bricks made of 100 % fly ash

A new approach to the production of bricks was carried out by using 100% lignite fly ash. The possibility of fly ash for use as building material was investigated. Pure fly ash and certain amount of mixing water (17.5 mass%) were used as body composition for the production of brick samples. This work studied the influence of treatments of fly ash, so called, sieved –63+40 µm fly ash, sieved –40 µm fly ash, ground 5h fly ash and ground 10h fly ash on mechanical properties. Test pieces made of –40 µm fly ash showed the superlative strength and were found to be superior in mechanical strength, especially in compressive strength as compared to red-fired clay brick, to common clay bricks and to facing bricks daily used in constructional work. The samples made of other types of fly ashes, in addition, can be superior to red-fired clay bricks and common clay bricks. Other brick properties can reach the specifications as required by market demands.
Two novel mutations in ERCC6 cause Cockayne syndrome B in a Chinese family

Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized principally by progressive growth failure, neurologic abnormality and premature aging. Mutations of excision repair cross-complementation group 6 (ERCC6) and ERCC8 are predominantly responsible for CS, of which mutation of ERCC6 accounts for approximately two thirds of cases. The current report describes two siblings with severe neurologic abnormality and premature aging. Whole exome sequencing identified two novel mutations in ERCC6 that had not been previously reported. One was a nonsense mutation at codon 612 in exon 9 (c.1834C>T, p.Arg612Ter), and the other a missense mutation at codon 975 in exon 16 (c.2923C>T, p.Arg975Trp). Cosegregation analysis revealed c.1834C>T was paternal and c.2923C>T was maternal. A healthy baby with no mutated alleles was delivered based on prenatal diagnosis performed by genetic testing of amniocytes for the causative mutation. The present study will enrich the clinical and genetic spectrum of CS in China and world wide, and provides more evidence for future genotype-phenotype studies.
Changes in access to primary care in Europe and its patterning, 2007–12: a repeated cross-sectional study

Background The strengthening of primary care (PC) has been encouraged as a strategy to achieve more efficient and equitable health systems. However, the Great Recession may have reduced access to PC. This paper analyses the change in access to PC and its patterning in 28 European countries between 2007 and 2012. Methods We used data from the 2007 and 2012 waves of the EU-SILC questionnaire (n = 687 170). The dependent variable was the self-reported access to PC ('easy' vs. 'difficult'). We modelled the access to PC as a function of the year and individual socioeconomic and country-level health system variables, using a mixed effects logistic regression, adjusting for sex, age, civil status, country of birth, chronic condition and self-reported health. Additionally, we interacted the year with socioeconomic and country-level variables. Results The probability of reporting difficult access to PC services was 4% lower in 2012, in comparison with 2007 (OR = 0.96, P < 0.01). People with the lowest educational level (OR = 1.63, P < 0.01), high difficulty to make ends meet (OR = 1.94, P < 0.01) and with material deprivation (OR = 1.25, P < 0.01) experienced a significantly higher likelihood of difficult access. The better access in 2012 was significantly higher in people living in countries with higher health expenditures, a greater number of generalist medical practitioners, and with stronger gatekeeping. Conclusion Access to PC improved between 2007 and 2012, and this improvement was greater for people living in countries with a higher investment in health and PC. However, the poor access amongst low-SE status people was stable over the period.
Coupled Dynamics of Iron and Phosphorus in Sediments of an Oligotrophic Coastal Basin and the Impact of Anaerobic Oxidation of Methane

Studies of phosphorus (P) dynamics in surface sediments of lakes and coastal seas typically emphasize the role of coupled iron (Fe), sulfur (S) and P cycling for sediment P burial and release. Here, we show that anaerobic oxidation of methane (AOM) also may impact sediment P cycling in such systems. Using porewater and sediment profiles for sites in an oligotrophic coastal basin (Bothnian Sea), we provide evidence for the formation of Fe-bound P (possibly vivianite; Fe3(PO4)2 . 8H2O) below the zone of AOM with sulfate. Here, dissolved Fe2+ released from oxides is no longer scavenged by sulfide and high concentrations of both dissolved Fe2+ (>1 mM) and PO4 in the porewater allow supersaturation with respect to vivianite to be reached. Besides formation of Fe(II)-P, preservation of Fe-oxide bound P likely also contributes to permanent burial of P in Bothnian Sea sediments. Preliminary budget calculations suggest that the burial of Fe-bound P allows these sediments to act as a major sink for P from the adjacent eutrophic Baltic Proper.
Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence

Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1′s regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence. Mcl-1′s anti-senescence activity also involves the unique ability to inhibit ROS formation by preventing the upregulation of pro-oxidants. Specifically, we found that NADPH oxidases (NOXs) are regulated by Mcl-1 and that NOX4 expression in particular is a required step for CIS induction that is blocked by Mcl-1. Lastly, we illustrate that by preventing expression of NOX4, Mcl-1 limits its availability in the mitochondria, thereby lowering the production of mitochondrial ROS during CIS. Our studies not only define the essential role of Mcl-1 in chemoresistance, but also for the first time link a key pro-survival Bcl-2 family member with the NOX protein family, both of which have significant ramifications in cancer progression.
ZEAXANTHIN EPOXIDASE Activity Potentiates Carotenoid Degradation in Maturing Seed1[OPEN]

Zeaxanthin epoxidase-dependent epoxidation of carotenoids accelerates degradation by carotenoid cleavage enzymes during late seed Arabidopsis maturation and seed desiccation. Elucidation of the carotenoid biosynthetic pathway has enabled altering the composition and content of carotenoids in various plants, but to achieve desired nutritional impacts, the genetic components regulating carotenoid homeostasis in seed, the plant organ consumed in greatest abundance, must be elucidated. We used a combination of linkage mapping, genome-wide association studies (GWAS), and pathway-level analysis to identify nine loci that impact the natural variation of seed carotenoids in Arabidopsis (Arabidopsis thaliana). ZEAXANTHIN EPOXIDASE (ZEP) was the major contributor to carotenoid composition, with mutants lacking ZEP activity showing a remarkable 6-fold increase in total seed carotenoids relative to the wild type. Natural variation in ZEP gene expression during seed development was identified as the underlying mechanism for fine-tuning carotenoid composition, stability, and ultimately content in Arabidopsis seed. We previously showed that two CAROTENOID CLEAVAGE DIOXYGENASE enzymes, CCD1 and CCD4, are the primary mediators of seed carotenoid degradation, and here we demonstrate that ZEP acts as an upstream control point of carotenoid homeostasis, with ZEP-mediated epoxidation targeting carotenoids for degradation by CCD enzymes. Finally, four of the nine loci/enzymatic activities identified as underlying natural variation in Arabidopsis seed carotenoids also were identified in a recent GWAS of maize (Zea mays) kernel carotenoid variation. This first comparison of the natural variation in seed carotenoids in monocots and dicots suggests a surprising overlap in the genetic architecture of these traits between the two lineages and provides a list of likely candidates to target for selecting seed carotenoid variation in other species.
“Should I Stay or Should I Go?”

Against the background of the crisis in the journalism industry, many journalists have decided to leave the occupation for other activities. We examine the reasons journalists give for leaving journalism, or remaining in it; the exit mechanisms they use; the destinations they choose and broader repercussions for Israeli journalism and the cultural industries. We base this examination on a sample of 60 life histories of active and former Israeli journalists, analyzed through the use of the “Exit, Voice and Loyalty” (EVL) typology developed by Albert Hirschman. Additionally, we investigate specific exit mechanisms and destinations using Bourdieu's notions of capital. We argue that applying the EVL typology to the data suggests the easy availability of exit routes out of journalism together with journalists' difficulty in voicing their occupational concerns within news organizations, given their chaotic organizational structure, contributed to news organizations' passive response to the crisis.
Contrast-enhanced computed tomography plus gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging for gross classification of hepatocellular carcinoma

Accurate gross classification through imaging is critical for determination of hepatocellular carcinoma (HCC) patient prognoses and treatment strategies. The present retrospective study evaluated the utility of contrast-enhanced computed tomography (CE-CT) combined with gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) for diagnosis and classification of HCCs prior to surgery. Ninety-four surgically resected HCC nodules were classified as simple nodular (SN), SN with extranodular growth (SN-EG), confluent multinodular (CMN), or infiltrative (IF) types. SN-EG, CMN and IF samples were grouped as non-SN. The abilities of the two imaging modalities to differentiate non-SN from SN HCCs were assessed using the EOB-MRI hepatobiliary phase and CE-CT arterial, portal, and equilibrium phases. Areas under the ROC curves for non-SN diagnoses were 0.765 (95% confidence interval [CI]: 0.666–0.846) for CE-CT, 0.877 (95% CI: 0.793–0.936) for EOB-MRI, and 0.908 (95% CI: 0.830–0.958) for CE-CT plus EOB-MRI. Sensitivities, specificities, and accuracies with respect to identification of non-SN tumors of all sizes were 71.4%, 81.6%, and 75.5% for CE-CT; 96.4%, 78.9%, and 89.3% for EOB-MRI; and 98.2%, 84.2%, and 92.5% for CE-CT plus EOB-MRI. These results show that CE-CT combined with EOB-MRI offers a more accurate imaging evaluation for HCC gross classification than either modality alone.
In Pursuit of Anchoring Vignettes That Work: Evaluating Generality Versus Specificity in Vignette Texts

Objective Anchoring vignettes appear with growing frequency in surveys of health and aging, but little research investigates how to optimize their wording. This study experimentally tests whether mentioning specific health conditions and/or medical procedures enhances or undermines vignette validity. Methods Three series of general health anchoring vignettes were fielded to 2,550 respondents in the Wisconsin Longitudinal Study: one mentioning no specific health conditions or procedures, one mentioning heart disease-related ones, and one mentioning diabetes-related ones. Variations on hierarchical ordered probit models were used to test whether vignette wording affected adherence to the key measurement assumptions of vignette equivalence (VE) and response consistency (RC). Results While all vignette series showed substantial violations of VE, violations were larger (especially by sex and education) when using disease-specific texts. RC violations appeared relatively minor, but somewhat larger in disease-specific texts. Discussion These findings suggest that more general, universal vignette texts may be preferable to ones describing highly specific conditions/procedures. The common advice to prioritize specificity and concreteness in survey texts may be misguided if sociodemographic groups differ in their familiarity or associations with the presented details. Anchoring vignettes are a potentially useful survey tool, but further efforts are needed to optimize their wording.
Physical forcing and physical/biochemical variability of the Mediterranean Sea: a review of unresolved issues and directions for future research

Abstract. This paper is the outcome of a workshop held in Rome in November 2011 on the occasion of the 25th anniversary of the POEM (Physical Oceanography of the Eastern Mediterranean) program. In the workshop discussions, a number of unresolved issues were identified for the physical and biogeochemical properties of the Mediterranean Sea as a whole, i.e., comprising the Western and Eastern sub-basins. Over the successive two years, the related ideas were discussed among the group of scientists who participated in the workshop and who have contributed to the writing of this paper. Three major topics were identified, each of them being the object of a section divided into a number of different sub-sections, each addressing a specific physical, chemical or biological issue: 1. Assessment of basin-wide physical/biochemical properties, of their variability and interactions. 2. Relative importance of external forcing functions (wind stress, heat/moisture fluxes, forcing through straits) vs. internal variability. 3. Shelf/deep sea interactions and exchanges of physical/biogeochemical properties and how they affect the sub-basin circulation and property distribution. Furthermore, a number of unresolved scientific/methodological issues were also identified and are reported in each sub-section after a short discussion of the present knowledge. They represent the collegial consensus of the scientists contributing to the paper. Naturally, the unresolved issues presented here constitute the choice of the authors and therefore they may not be exhaustive and/or complete. The overall goal is to stimulate a broader interdisciplinary discussion among the scientists of the Mediterranean oceanographic community, leading to enhanced collaborative efforts and exciting future discoveries.
Efficient Inexact Proximal Gradient Algorithm for Nonconvex Problems

While proximal gradient algorithm is originally designed for convex optimization, several variants have been recently proposed for nonconvex problems. Among them, nmAPG [Li and Lin, 2015] is the state-of-art. However, it is inefficient when the proximal step does not have closed-form solution, or such solution exists but is expensive, as it requires more than one proximal steps to be exactly solved in each iteration. In this paper, we propose an efficient accelerate proximal gradient (niAPG) algorithm for nonconvex problems. In each iteration, it requires only one inexact (less expensive) proximal step. Convergence to a critical point is still guaranteed, and a O(1/k) convergence rate is derived. Experiments on image inpainting and matrix completion problems demonstrate that the proposed algorithm has comparable performance as the state-of-the-art, but is much faster.
Fundamental limits on dynamic inference from single-cell snapshots

Significance Seeing a snapshot of individuals at different stages of a dynamic process can reveal what the process would look like for a single individual over time. Biologists apply this principle to infer temporal sequences of gene expression states in cells from measurements made at a single moment in time. However, the sparsity and high dimensionality of single-cell data have made inference difficult using formal approaches. Here, we apply recent innovations in spectral graph theory to devise a simple and asymptotically exact algorithm for inferring the unique dynamic solution under defined approximations and apply it to data from bone marrow stem cells. Single-cell expression profiling reveals the molecular states of individual cells with unprecedented detail. Because these methods destroy cells in the process of analysis, they cannot measure how gene expression changes over time. However, some information on dynamics is present in the data: the continuum of molecular states in the population can reflect the trajectory of a typical cell. Many methods for extracting single-cell dynamics from population data have been proposed. However, all such attempts face a common limitation: for any measured distribution of cell states, there are multiple dynamics that could give rise to it, and by extension, multiple possibilities for underlying mechanisms of gene regulation. Here, we describe the aspects of gene expression dynamics that cannot be inferred from a static snapshot alone and identify assumptions necessary to constrain a unique solution for cell dynamics from static snapshots. We translate these constraints into a practical algorithmic approach, population balance analysis (PBA), which makes use of a method from spectral graph theory to solve a class of high-dimensional differential equations. We use simulations to show the strengths and limitations of PBA, and then apply it to single-cell profiles of hematopoietic progenitor cells (HPCs). Cell state predictions from this analysis agree with HPC fate assays reported in several papers over the past two decades. By highlighting the fundamental limits on dynamic inference faced by any method, our framework provides a rigorous basis for dynamic interpretation of a gene expression continuum and clarifies best experimental designs for trajectory reconstruction from static snapshot measurements.