Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes

Aim: The aim of the study was to investigate the role of Humphrey Matrix threshold testing in the detection of early functional retinal impairment in subjects with type 1 diabetes mellitus (DM1) without any signs of retinal vasculopathy, and to investigate the relationship between both functional and structural retinal parameters and metabolic control. Methods: Thirty eyes of 30 subjects with DM1, with no sign of retinal vasculopathy, and 30 eyes of 30 age- and sex-matched healthy subjects were enrolled in this cross-sectional clinical study. Functional testing included Humphrey Matrix perimetry and white-on-white Humphrey visual field perimetry (HFA), while retinal nerve fibre layer (RNFL) thickness was measured by scanning laser polarimetry with variable corneal birefringence compensator (GDx VCC). Results: Matrix mean deviation (MD) was found to be significantly reduced in subjects with DM1 compared with controls (−1.10 (SD 2.98; 95% CI −2.21 to 0.01) vs 1.37 (SD 2.11; 95% CI 0.58 to 2.16), p = 0.0005). HFA MD and pattern standard deviation (PSD) were significantly worse in subjects with DM1 compared with controls (p = 0.010 and p = 0.013 respectively). Among structural parameters, average peripapillary RNFL thickness was reduced in DM1 subjects (p = 0.006). Matrix MD and HFA MD and PSD, and average peripapillary and superior RNFL, were significantly reduced in subjects with DM1 with HbA1c ⩾7% compared with controls. Conclusions: Functional and structural retinal testing by Humphrey Matrix and GDx VCC could be useful for the identification of early retinal impairment in people with DM1 with no sign of retinal vasculopathy.
Fast Mining of Iceberg Lattices: A Modular Approach Using Generators

Beside its central place in FCA, the task of constructing the concept lattice, i.e., concepts plus Hasse diagram, has attracted some interest within the data mining (DM) field, primarily to support the mining of association rule bases. Yet most FCA algorithms do not pass the scalability test fundamental in DM. We are interested in the ice- berg part of the lattice, alias the frequent closed itemsets (FCIs) plus precedence, augmented with the respective generators (FGs) as these provide the starting point for nearly all known bases. Here, we investi- gate a modular approach that follows a workflow of individual tasks that diverges from what is currently practiced. A straightforward instantia- tion thereof, Snow-Touch, is presented that combines past contributions of ours, Touch for FCIs/FGs and Snow for precedence. A performance comparison of Snow-Touch to its closest competitor, Charm-L, indicates that in the specific case of dense data, the modularity overhead is oset by the speed gain of the new task order. To demonstrate our method's usefulness, we report first results of a genome data analysis application.
Update on therapeutic management of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive diffuse parenchymal lung disease of unknown origin, with a mortality rate exceeding that of many cancers. The diagnostic process is complex and relies on the clinician integrating clinical, laboratory, radiological, and histological data. In the last decade, major advances in our understanding of the pathogenesis of IPF have shifted the paradigm from a primarily inflammatory process evolving to fibrosis to a condition driven by aberrant wound healing following alveolar epithelial cell injury that results in scarring of the lung, architectural distortion, and irreversible loss of function. Improved understanding of disease pathogenesis has led to the identification of several therapeutic targets and the design of high-quality clinical trials evaluating novel compounds. However, the results of these studies have been mostly disappointing, probably due to the plethora of mediators, growth factors, and signaling pathways involved in the fibrotic process. Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough. Nevertheless, we still have a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of concomitant conditions and physical debility, as well as timely referral for lung transplantation, remains essential. Several agents with a high potential are currently being tested, and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.
Characterization of SpPol4, a unique X-family DNA polymerase in Schizosaccharomyces pombe

As predicted by the amino acid sequence, the purified protein coded by Schizosaccharomyces pombe SPAC2F7.06c is a DNA polymerase (SpPol4) whose biochemical properties resemble those of other X family (PolX) members. Thus, this new PolX is template-dependent, polymerizes in a distributive manner, lacks a detectable 3′→5′ proofreading activity and its preferred substrates are small gaps with a 5′-phosphate group. Similarly to Polμ, SpPol4 can incorporate a ribonucleotide (rNTP) into a primer DNA. However, it is not responsible for the 1–2 rNTPs proposed to be present at the mating-type locus and those necessary for mating-type switching. Unlike Polμ, SpPol4 lacks terminal deoxynucleotidyltransferase activity and realigns the primer terminus to alternative template bases only under certain sequence contexts and, therefore, it is less error-prone than Polμ. Nonetheless, the biochemical properties of this gap-filling DNA polymerase are suitable for a possible role of SpPol4 in non-homologous end-joining. Unexpectedly based on sequence analysis, SpPol4 has deoxyribose phosphate lyase activity like Polβ and Polλ, and unlike Polμ, suggesting also a role of this enzyme in base excision repair. Therefore, SpPol4 is a unique enzyme whose enzymatic properties are hybrid of those described for mammalian Polβ, Polλ and Polμ.
Anti-self-dual four–manifolds with a parallel real spinor

Anti–self–dual metrics in the (++ ––) signature that admit a covariantly constant real spinor are studied. It is shown that finding such metrics reduces to solving a fourth–order integrable partial differential equation (PDE), and some examples are given. The corresponding twistor space is characterized by existence of a preferred non–zero real section of κ–1/4, where κ is the canonical line bundle of the twistor space. It is demonstrated that if the parallel spinor is preserved by a Killing vector, then the fourth–order PDE reduces to the dispersionless Kadomtsev–Petviashvili equation and its linearization. Einstein–Weyl structures on the space of trajectories of the symmetry are characterized by the existence of a parallel weighted null vector.
Role of IME1 expression in regulation of meiosis in Saccharomyces cerevisiae

Two signals are required for meiosis and spore formation in the yeast Saccharomyces cerevisiae: starvation and the MAT products a1 and alpha 2, which determine the a/alpha cell type. These signals lead to increased expression of the IME1 (inducer of meiosis) gene, which is required for sporulation and sporulation-specific gene expression. We report here the sequence of the IME1 gene and the consequences of IME1 expression from the GAL1 promoter. The deduced IME1 product is a 360-amino-acid protein with a tyrosine-rich C-terminal region. Expression of PGAL1-IME1 in vegetative a/alpha cells led to moderate accumulation of four early sporulation-specific transcripts (IME2, SPO11, SPO13, and HOP1); the transcripts accumulated 3- to 10-fold more after starvation. Two sporulation-specific transcripts normally expressed later (SPS1 and SPS2) did not accumulate until PGAL1-IME1 strains were starved, and the intact IME1 gene was not activated by PGAL1-IME1 expression. In a or alpha cells, which lack alpha 2 or a1, expression of PGAL1-IME1 led to the same pattern of IME2 and SPO13 expression as in a/alpha cells, as measured with ime2::lacZ and spo13::lacZ fusions. Thus, in wild-type strains, the increased expression of IME1 in starved a/alpha cells can account entirely for cell type control, but only partially for nutritional control, of early sporulation-specific gene expression. PGAL1-IME1 expression did not cause growing cells to sporulate but permitted efficient sporulation of amino acid-limited cells, which otherwise sporulated poorly. We suggest that IME1 acts primarily as a positive regulator of early sporulation-specific genes and that growth arrest is an independent prerequisite for execution of the sporulation program.
Meta-analysis: Excess Mortality After Hip Fracture Among Older Women and Men

BACKGROUND Although an increased risk for death after hip fracture is well established, whether this excess mortality persists over time is unclear. PURPOSE To determine the magnitude and duration of excess mortality after hip fracture in older men and women. DATA SOURCES Electronic search of MEDLINE and EMBASE for English and non-English articles from 1957 to May 2009 and manual search of article references. STUDY SELECTION Prospective cohort studies were selected by 2 independent reviewers. The studies had to assess mortality in women (22 cohorts) or men (17 cohorts) aged 50 years or older with hip fracture, carry out a life-table analysis, and display the survival curves of the hip fracture group and age- and sex-matched control groups. DATA EXTRACTION Survival curve data and items relevant to study validity and generalizability were independently extracted by 2 reviewers. DATA SYNTHESIS Time-to-event meta-analyses showed that the relative hazard for all-cause mortality in the first 3 months after hip fracture was 5.75 (95% CI, 4.94 to 6.67) in women and 7.95 (CI, 6.13 to 10.30) in men. Relative hazards decreased substantially over time but did not return to rates seen in age- and sex-matched control groups. Through use of life-table methods, investigators estimated that white women having a hip fracture at age 80 years have excess annual mortality compared with white women of the same age without a fracture of 8%, 11%, 18%, and 22% at 1, 2, 5, and 10 years after injury, respectively. Men with a hip fracture at age 80 years have excess annual mortality of 18%, 22%, 26%, and 20% at 1, 2, 5, and 10 years after injury, respectively. LIMITATIONS Cohort studies varied, sometimes markedly, in size, duration of observation, selection of control populations, ascertainment of death, and adjustment for comorbid conditions. Only published data that displayed findings with survival curves were examined. Publication bias was possible. CONCLUSION Older adults have a 5- to 8-fold increased risk for all-cause mortality during the first 3 months after hip fracture. Excess annual mortality persists over time for both women and men, but at any given age, excess annual mortality after hip fracture is higher in men than in women. PRIMARY FUNDING SOURCE Fund for Scientific Research and Willy Gepts Foundation, Universitair Ziekenhuis Brussel.
Evidence supporting paracrine hypothesis for Akt‐modified mesenchymal stem cell‐mediated cardiac protection and functional improvement

We previously reported that intramyocardial injection of bone marrow‐derived mesenchymal stem cells overexpressing Akt (Akt‐MSCs) inhibits ventricular remodeling and restores cardiac function measured 2 wk after myocardial infarction. Here, we report that the functional improvement occurs in < 72 h. This early remarkable effect cannot be readily attributed to myocardial regeneration from the donor cells. Thus, we hypothesized that paracrine actions exerted by the cells through the release of soluble factors might be important mechanisms of tissue repair and functional improvement after injection of the Akt‐MSCs. Indeed, in the current study we demonstrate that conditioned medium from hypoxic Akt‐MSCs markedly inhibits hypoxia‐induced apoptosis and triggers vigorous spontaneous contraction of adult rat cardiomyocytes in vitro. When injected into infarcted hearts, the Akt‐MSC conditioned medium significantly limits infarct size and improves ventricular function relative to controls. Sup‐port to the paracrine hypothesis is provided by data showing that several genes, coding for factors (VEGF, FGF‐2, HGF, IGF‐I, and TB4) that are potential mediators of the effects exerted by the Akt‐MSC conditioned medium, are significantly up‐regulated in the Akt‐MSCs, particularly in response to hypoxia. Taken together, our data support Akt‐MSC‐mediated para‐crine mechanisms of myocardial protection and functional improvement. ‐Gnecchi, M. , He, H. , Noiseux, N. , Liang, O. D. , Zhang, L. , Morello, F. , Mu, H. , Melo, L. G. , Pratt, R. E. , Ingwall, J. S. , Dzau, V. J. Evidence supporting paracrine hypothesis for Akt‐modified mes‐enchymal stem cell‐mediated cardiac protection and functional improvement. FASEB J. 20, 661–669 (2006)
Particle‐mediated gene therapy of wounds

Gene therapy is becoming a reality, and it is a particularly attractive approach for wound healing, because the wound site is often exposed, the treatment and condition should be transient, and gene products such as growth factors and cytokines suffer from problems with bioavailability and stability. Among the techniques for gene delivery to the wound site, particle‐mediated bombardment with a device called the gene gun has become an important developmental tool. This instrument has been used in numerous examples of wound gene therapy with growth factors or their receptors in the last decade. Among the advantages of particle‐mediated bombardment are ease and speed of preparation of the delivery vehicle, the stability of the DNA preparation, the absence of (viral) antigens, the ability to target the projectiles to different tissue depths and areas, and the rapid shedding of both particles and DNA if they are targeted to the epidermis. Clinical application of the technology remains limited by the relatively low efficiency of the method, the potential tissue damage created by impact of the particles, and the coverage area. The gene gun can also be used to facilitate the discovery and validation of gene products as wound healing agents.
Trading representability for scalability: adaptive multi-hyperplane machine for nonlinear classification

Support Vector Machines (SVMs) are among the most popular and successful classification algorithms. Kernel SVMs often reach state-of-the-art accuracies, but suffer from the curse of kernelization due to linear model growth with data size on noisy data. Linear SVMs have the ability to efficiently learn from truly large data, but they are applicable to a limited number of domains due to low representational power. To fill the representability and scalability gap between linear and nonlinear SVMs, we propose the Adaptive Multi-hyperplane Machine (AMM) algorithm that accomplishes fast training and prediction and has capability to solve nonlinear classification problems. AMM model consists of a set of hyperplanes (weights), each assigned to one of the multiple classes, and predicts based on the associated class of the weight that provides the largest prediction. The number of weights is automatically determined through an iterative algorithm based on the stochastic gradient descent algorithm which is guaranteed to converge to a local optimum. Since the generalization bound decreases with the number of weights, a weight pruning mechanism is proposed and analyzed. The experiments on several large data sets show that AMM is nearly as fast during training and prediction as the state-of-the-art linear SVM solver and that it can be orders of magnitude faster than kernel SVM. In accuracy, AMM is somewhere between linear and kernel SVMs. For example, on an OCR task with 8 million highly dimensional training examples, AMM trained in 300 seconds on a single-core processor had 0.54% error rate, which was significantly lower than 2.03% error rate of a linear SVM trained in the same time and comparable to 0.43% error rate of a kernel SVM trained in 2 days on 512 processors. The results indicate that AMM could be an attractive option when solving large-scale classification problems. The software is available at www.dabi. temple.edu/~vucetic/AMM.html.
A Simple Coarse-Grained Model of a Carbon Nanotube Forest Interacting with a Rigid Substrate

Carbon nanotubes (CNTs) exhibit exceptional thermal, mechanical, and electronic properties and hence are of interest for potential applications in novel materials and devices. To develop these applications, researchers must achieve a better understanding of how to process and manipulate CNTs at the nanoscale. Toward this goal, here we propose a coarse-grained model to describe the mechanical response of a CNT forest compressed between two rigid substrates. We use the model to make qualitative and quantitative predictions and to conduct a set of parametric studies. The behavior of the system observed in these studies qualitatively matches the experiments on surface adhesion.
Strategies for the management of OHSS: Results from freezing-all cycles.

OBJECTIVE To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. METHODS The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. RESULTS A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. CONCLUSION The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.
Stretchable Optical Fibers: Threads for Strain‐Sensitive Textiles

Soft, stretchable, sewable, and strain‐sensitive optical fibers are reported. Intrinsically stretchable optical waveguides capable of >100% strain are formed by coating a commercially available elastic urethane fiber (“Stretch Magic”) with a silicone cladding having a lower refractive index. These 1–2 mm diameter fibers can be attached to textiles using a sewing machine. Because the attaching threads create microbends in the fiber, the sewn fibers are prestrained for monotonic intensity‐versus‐strain behavior. Installed in a stretchable piece of athletic tape, they detect strains originating from changing muscle shapes during weight‐bearing activity.
Superconducting Properties of Nb 3 Sn Wires with Radially Arranged Filament Development that Realizes High J c and Low Hysteresis Loss

Synopsis: An internal-tin route Nb3Sn superconducting wire that has both remarkably low hysteresis loss (Qh) and high critical -current density (Jc) was developed with a new design idea. The wire was constructed by arranging the filaments in a radial layout, enlarging the outer filaments along the radial direction, intentionally narrowing the filament spacing in the radial direction and enlarging the filament spacing in tangential direction. Thus, the electromagnetic combination among the filaments in tangential direction due to the bridging and/or proximity effect was suppressed without decreasing the volume fraction of Nb. As a result, excellent properties such as Jc(12 T)= 1.15�10 A/mm and Qh=301 mJ/cm (for 1 cycle of B=±3 T) were obtained. We also evaluated the transition temperature (Tc) and upper critical field (Bc2) of the wire. The values for Tc and Bc2 were 17.3 K and 24.1 T, respectively, which were much better than those of usual internal-tin route wires. Electron probe micro-analyses confirmed that the good Tc and Bc2 were the result of the qualitative improvement in the Nb3Sn compound based on the effects of arranging the Nb filaments radially, increasing the ratio of Sn-to-Nb and shortening the diffusion length for Sn due to the increase of the module number. This wire is promising for use with conduction-cooled high-field magnets, in which there is a need to decrease the load of the cryocooler, and also for the strands of fusion coils.
Herbivore-Induced Callose Deposition on the Sieve Plates of Rice: An Important Mechanism for Host Resistance1[W][OA]

The brown planthopper (Nilaparvata lugens Stål; BPH) is a specialist herbivore on rice (Oryza sativa) that ingests phloem sap from the plant through its stylet mouthparts. Electronic penetration graphs revealed that BPH insects spent more time wandering over plants carrying the resistance genes Bph14 and Bph15, but less time ingesting phloem than they did on susceptible plants. They also showed that their feeding was frequently interrupted. Tests with [14C]sucrose showed that insects ingested much less phloem sap from the resistant than the susceptible plants. BPH feeding up-regulated callose synthase genes and induced callose deposition in the sieve tubes at the point where the stylet was inserted. The compact callose remained intact in the resistant plants, but genes encoding β-1,3-glucanases were activated, causing unplugging of the sieve tube occlusions in susceptible plants. Continuing ingestion led to a remarkable reduction in the susceptible plants' sucrose content and activation of the RAmy3D gene, leading to starch hydrolysis and ultimately carbohydrate deprivation in the plants. Our results demonstrate that BPH feeding induces the deposition of callose on sieve plates in rice and that this is an important defense mechanism that prevents insects from ingesting phloem sap. In response, however, the BPH can unplug sieve tube occlusions by activating β-1,3-glucanase genes in rice plants.
Platform Ecosystems: How Developers Invert the Firm

For a period starting in 2015, Apple, Google, and Microsoft became the most valuable companies in the world. Each was marked by an external developer ecosystem. Anecdotally, at least, developers matter. Using a formal model of code spillovers, we show how a rising number of developers can invert the firm. That is, firms will choose to innovate using open external contracts in preference to closed vertical integration. The locus of value creation moves from inside the firm to outside. Distinct from physical goods, digital goods afford firms the chance to optimize spillovers. Further, firms that pursue high risk innovations with more developers can be more profitable than firms that pursue low risk innovations with fewer developers. More developers give platform firms more chances at success. Our contribution is to show why developers might cause a shift in organizational form and to provide a theory of how platform firms optimize their own intellectual property regimes in order to maximize growth. We use stylized facts from multiple platform firms to illustrate our theory and results.