Miracle-dz/UniFAR-FTUs huggingface dataset:
Adherence to the American Diabetes Association retinal screening guidelines for population with diabetes in the United States

ABSTRACT Purpose: (1) To assess long-term adherence to American Diabetes Association guideline-recommended retinal screening among population with diabetes in the United States. (2) To determine factors associated with long-term adherence to routine eye screening exams. Methods: A retrospective cohort study was conducted in adult patients with diabetes identified from January 2009 to December 2010. Patients were followed until disenrollment, death, or study end date (December 2013). A patient was defined as adherent when having at least one exam in each 12-month period if there was evidence of retinopathy, or at least one exam in each 24-month period if there was no evidence of retinopathy. Multivariate logistic regressions were used to investigate patient demographics and other baseline characteristics associated with adherence to guidelines. Results: A total of 204,073 patients were identified; the mean age (SD) was 61 (13) years and 48% were female. Overall, 71.1% were adherent to the retinal screening guidelines during a median of 4.8 years of follow-up including 27.7% who received an eye exam every year. Patient socioeconomic status (younger age, black race, lower income/education), less comorbidity, insulin use, higher specialist copayment plans, and proxies for poor patient behavior (lower adherence to the oral hypoglycemic agents, less diabetes education, hemoglobin A1C >9%) were associated with nonadherence to routine eye screening exams. Conclusion: During nearly 5 years of follow-up, 28.9% of patients with diabetes were nonadherent to the retinal screening guidelines. Future research should focus on the development of interventions to address modifiable factors associated with nonadherence.
Emergency Services of Viral RNAs: Repair and Remodeling

SUMMARY Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.
1 Agrobacterium-Mediated Transformation of Wheat : General Overview and New Approaches to Model and Identify the Key Factors Involved

Wheat is the world’s second largest crop, supplying 19% of human calories; the largest volume crop traded internationally and grown on approximately 17% of the world’s cultivatable land (over 200 million hectares) (Jones, 2005; Atchison et al., 2010). However, probably due to climate change, some adverse environmental conditions have caused a downward trend in world wheat production (FAO, 2003; 2011). In this context, developing new higher yielding wheat varieties more tolerant or resistant to abiotic and/or biotic stress, using all available plant biotechnology technologies available, should be considered as the major challenge.
A functional polymorphism in the pre‐miR‐146a gene is associated with the risk of nonsyndromic orofacial cleft

microRNAs (miRNAs) are widely involved in craniofacial development, and genetic variants of miRNAs may be associated with the risk of nonsyndromic orofacial cleft (NSOC). Here, we systematically selected five single nucleotide polymorphisms (SNPs) of miRNAs and investigated the associations between these variants and NSOC susceptibility in a two‐stage case–control study including 1,406 NSOC patients and 1,578 controls from the Chinese population. We found that compared with the C allele, the rs2910164 G allele of pre‐miR‐146a was associated with an increased risk of NSOC (additive model: odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.06–1.30, P = 0.002), including both cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO). Bioinformatic prediction and functional assays revealed that the C allele of rs2910164 was significantly associated with inhibited HEK‐293 and HEPM cell proliferation and decreased abundance of TRAF6. Both miR‐146a and TRAF6 were expressed in the lip tissue samples of NSOC patients, and a moderate inverse correlation was observed between them. Taken together, these results demonstrated that miR‐146a/rs2910164 is associated with susceptibility to NSOC, providing novel insights into the genetic etiology and underlying biology of NSOC.
Role of oxidative stress in cataractogenesis

Background: Cataract is a multifactorial disease and is a major cause of blindness in india. Oxidative stress is thought to be a major factor to initiate the process of cataractogenesis. It is today well established fact that oxidative stress participates in both age-related (senile) and diabetes-induced cataract (diabetic). Oxidative damage to the lens most likely arises as a consequence of an impaired antioxidant defence system, due to increased generation of ROS both by age and diabetes. The present study was designed to determine role of oxidative stress in cataractogensis and to compare levels of oxidative stress markers in senile and diabetic cataract patients. Methods: Serum malondialdehyde (MDA) and serum protein carbonyl (PC) were measured as indicator of oxidative stress whereas antioxidant status was assessed by estimating serum Total antioxidant capacity (TAC) and dietary antioxidants levels i.e vitamin C and vitamin E in senile and diabetic cataract patients compared with healthy controls. Results: The result reveal that the serum MDA and PC levels were significantly increased in patients with senile and diabetic cataract whereas serum TAC, vitamin C and Vitamin E were significantly reduced in senile and diabetic patients when compared with normal healthy controls. Conclusions: From the result, it is concluded that oxidative stress is in the foreground of cataract formation which includes senile and diabetic cataract. Oxidative stress produced in diabetic cataract patients is more as compared to senile cataract patients.
An approximate minimum variance filter for nonlinear systems with randomly delayed observations

In this paper, we extend our earlier results on minimum variance filter for systems with additive multiplicative noise in two different ways. Firstly, we propose a novel characterization of the linearization error in terms of multiplicative noise. Secondly, we also allow for random delay of up to one time step in the measurement. The delay is modelled by Bernoulli random variables. We derive a closed-form expression for the minimum variance filter for the resulting system with a linearized state transition equation, accounting for both the linearization error as well as the random delay. The utility of the proposed filtering algorithm is demonstrated through numerical experiments.
Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors

Background Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question. Methodology We conducted a Phase Ia, non-randomized clinical trial in 16 healthy, malaria-naïve adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding two alleles (3D7 and FVO) of the P. falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1). ChAd63-MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing high-level T cell responses to both alleles 3D7 (median 2036 SFU/million PBMC) and FVO (median 1539 SFU/million PBMC), with a mixed CD4+/CD8+ phenotype, as well as substantial AMA1-specific serum IgG responses (medians of 49 µg/mL and 41 µg/mL for 3D7 and FVO AMA1 respectively) that demonstrated growth inhibitory activity in vitro. Conclusions ChAd63-MVA is a safe and highly immunogenic delivery platform for both alleles of the AMA1 antigen in humans which warrants further efficacy testing. ChAd63-MVA is a promising heterologous prime-boost vaccine strategy that could be applied to numerous other diseases where strong cellular and humoral immune responses are required for protection. Trial Registration ClinicalTrials.gov NCT01095055
Development of Multisensory Reweighting Is Impaired for Quiet Stance Control in Children with Developmental Coordination Disorder (DCD)

Background Developmental Coordination Disorder (DCD) is a leading movement disorder in children that commonly involves poor postural control. Multisensory integration deficit, especially the inability to adaptively reweight to changing sensory conditions, has been proposed as a possible mechanism but with insufficient characterization. Empirical quantification of reweighting significantly advances our understanding of its developmental onset and improves the characterization of its difference in children with DCD compared to their typically developing (TD) peers. Methodology/Principal Findings Twenty children with DCD (6.6 to 11.8 years) were tested with a protocol in which visual scene and touch bar simultaneously oscillateded medio-laterally at different frequencies and various amplitudes. Their data were compared to data on TD children (4.2 to 10.8 years) from a previous study. Gains and phases were calculated for medio-lateral responses of the head and center of mass to both sensory stimuli. Gains and phases were simultaneously fitted by linear functions of age for each amplitude condition, segment, modality and group. Fitted gains and phases at two comparison ages (6.6 and 10.8 years) were tested for reweighting within each group and for group differences. Children with DCD reweight touch and vision at a later age (10.8 years) than their TD peers (4.2 years). Children with DCD demonstrate a weak visual reweighting, no advanced multisensory fusion and phase lags larger than those of TD children in response to both touch and vision. Conclusions/Significance Two developmental perspectives, postural body scheme and dorsal stream development, are provided to explain the weak vision reweighting. The lack of multisensory fusion supports the notion that optimal multisensory integration is a slow developmental process and is vulnerable in children with DCD.
MULTIVARIATE AR SYSTEMS AND MIXED FREQUENCY DATA: G-IDENTIFIABILITY AND ESTIMATION

This paper is concerned with the problem of identifiability of the parameters of a high frequency multivariate autoregressive model from mixed frequency time series data. We demonstrate identifiability for generic parameter values using the population second moments of the observations. In addition we display a constructive algorithm for the parameter values and establish the continuity of the mapping attaching the high frequency parameters to these population second moments. These structural results are obtained using two alternative tools viz. extended Yule Walker equations and blocking of the output process. The cases of stock and flow variables, as well as of general linear transformations of high frequency data, are treated. Finally, we briefly discuss how our constructive identifiability results can be used for parameter estimation based on the sample second moments.
Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response

Abstract Transfer RNA-derived small RNAs (tsRNAs) are an emerging class of small RNAs, yet their regulatory roles have not been well understood. Here we studied the molecular mechanisms and consequences of tsRNA-mediated regulation in Drosophila. By analyzing 495 public small RNA libraries, we demonstrate that most tsRNAs are conserved, prevalent and abundant in Drosophila. By carrying out mRNA sequencing and ribosome profiling of S2 cells transfected with single-stranded tsRNA mimics and mocks, we show that tsRNAs recognize target mRNAs through conserved complementary sequence matching and suppress target genes by translational inhibition. The target prediction suggests that tsRNAs preferentially suppress translation of the key components of the general translation machinery, which explains how tsRNAs inhibit the global mRNA translation. Serum starvation experiments confirm tsRNAs participate in cellular starvation responses by preferential targeting the ribosomal proteins and translational initiation or elongation factors. Knock-down of AGO2 in S2 cells under normal and starved conditions reveals a dependence of the tsRNA-mediated regulation on AGO2. We also validated the repressive effects of representative tsRNAs on cellular global translation and specific targets with luciferase reporter assays. Our study suggests the tsRNA-mediated regulation might be crucial for the energy homeostasis and the metabolic adaptation in the cellular systems.
Sjögren Syndrome-Associated Small Fiber Neuropathy

AbstractWe conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjögren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy.SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 ± 13.1 years, and at SFN diagnosis, 58.9 ± 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients.Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 ± 13.1 vs. 49.5 ± 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005). In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with pSS-associated SFN are characterized by an older age at pSS diagnosis and a distinctive immunologic profile hallmarked by a lower frequency of serum B-cell activation markers.
Progressive Deformation of the Optic Nerve Head and Peripapillary Structures by Graded Horizontal Duction

Purpose We investigated the effect of graded range of horizontal duction on the shape of the peripapillary Bruch's membrane (ppBM) and optic nerve head (ONH). Methods In 50 eyes of 25 normal subjects, the ONH and peripapillary retina were imaged by optical coherence tomography (OCT) in central gaze and incremental angles of add- and abduction. Displacements of the Bruch's membrane opening (BMO), optic cup (OC), and change in ONH angle in eccentric gazes were compared to those of central gaze, in add- and abduction. Results With increasing duction, the nasal edge of the BMO (nBMO) shifted progressively anteriorly in adduction and posteriorly in abduction, while the temporal edge of the BMO (tBMO) shifted posteriorly in adduction and anteriorly in abduction. The summed absolute nBMO and tBMO displacements in 30° and 35° adduction significantly exceeded those in comparable abduction angles (P < 0.005 for both). The ONH progressively tilted temporally in adduction and nasally in abduction; absolute ONH tilt in adduction was significantly greater than that in abduction for 30° and 35° ductions (P < 0.005 for both). BMO displacement and ONH tilt in adduction exhibited bilinear behavior, with greater effects for both at angles exceeding 26°. The OC shifted significantly farther anteriorly in abduction than adduction at every angle from 10° to 35°. Conclusions Horizontal duction deforms the ONH and ppBM, but more in adduction than in abduction, and increasingly so for angles greater than 26°. This behavior is consistent with optic nerve sheath tethering for adduction exceeding 26°.
Evidence for the effectiveness of CME. A review of 50 randomized controlled trials.

OBJECTIVE To assess the impact of diverse continuing medical education (CME) interventions on physician performance and health care outcomes. DATA SOURCES Using continuing medical education and related phrases, we performed regular searches of the indexed literature (MEDLINE, Social Science Index, the National Technical Information Service, and Educational Research Information Clearinghouse) from 1975 through 1991. In addition, for these years, we used manual searches, key informants, and requests to authors to locate other indexed articles and the nonindexed literature of adult and continuing professional education. STUDY SELECTION From the resulting database we selected studies that met the following criteria: randomized controlled trials; educational programs, activities, or other interventions; studies that included 50% or more physicians; follow-up assessments of at least 75% of study subjects; and objective assessments of either physician performance or health care outcomes. DATA EXTRACTION Studies were reviewed for data related to physician specialty and setting. Continuing medical education interventions were classified by their mode(s) of activity as being predisposing, enabling, or facilitating. Using the statistical tests supplied by the original investigators, physician performance outcomes and patient outcomes were classified as positive, negative, or inconclusive. DATA SYNTHESIS We located 777 CME studies, of which 50 met all criteria. Thirty-two of these analyzed physician performance; seven evaluated patient outcomes; 11 examined both measures. The majority of the 43 studies of physician performance showed positive results in some important measures of resource utilization, counseling strategies, and preventive medicine. Of the 18 studies of health care outcomes, eight demonstrated positive changes in patients' health care outcomes. CONCLUSION Broadly defined CME interventions using practice-enabling or reinforcing strategies consistently improve physician performance and, in some instances, health care outcomes.
Abundant production of exopolysaccharide by EAEC strains enhances the formation of bacterial biofilms in contaminated sprouts

ABSTRACT Enteroaggregative E. coli (EAEC) is associated with food-borne outbreaks of diarrhea and growth faltering among children in developing countries. A Shiga toxin-producing EAEC strain of serotype O104:H4 strain caused one of the largest outbreaks of a food-borne infection in Europe in 2011. The outbreak was traced to contaminated fenugreek sprouts, yet the mechanisms whereby such persistent contamination of sprouts could have occurred are not clear. We found that under ambient conditions of temperature and in minimal media, pathogenic Shiga toxin-producing EAEC O104:H4 227-11 and non-Shiga toxin-producing 042 strains both produce high levels of exopolysaccharide structures (EPS) that are released to the external milieu. The exopolysaccharide was identified as colanic acid (CA). Unexpectedly, Shiga-toxin producing EAEC strain 227-11 produced 3-6-fold higher levels of CA than the 042 strain, suggesting differential regulation of the CA in the two strains. The presence of CA was accompanied by the formation of large biofilm structures on the surface of sprouts. The wcaF-wza chromosomal locus was required for the synthesis of CA in EAEC 042. Deletion in the glycosyltransferase wcaE gene abolished the production of CA in 042, and resulted in diminished adherence to sprouts when co-cultured at ambient temperature. In conclusion, this work suggests that copious production of CA may contribute to persistence of EAEC in the environment and suggests a potential explanation for the large Shiga toxin-producing EAEC outbreak in 2011.
Susceptibility and tolerance of rice crop to salt threat: Physiological and metabolic inspections

Salinity threat is estimated to reduce global rice production by 50%. Comprehensive analysis of the physiological and metabolite changes in rice plants from salinity stress (i.e. tolerant versus susceptible plants) is important to combat higher salinity conditions. In this study, we screened a total of 92 genotypes and selected the most salinity tolerant line (SS1-14) and most susceptible line (SS2-18) to conduct comparative physiological and metabolome inspections. We demonstrated that the tolerant line managed to maintain their water and chlorophyll content with lower incidence of sodium ion accumulation. We also examined the antioxidant activities of these lines: production of ascorbate peroxidase (APX) and catalase (CAT) were significantly higher in the sensitive line while superoxide dismutase (SOD) was higher in the tolerant line. Partial least squares discriminant analysis (PLS-DA) score plots show significantly different response for both lines after the exposure to salinity stress. In the tolerant line, there was an upregulation of non-polar metabolites and production of sucrose, GABA and acetic acid, suggesting an important role in salinity adaptation. In contrast, glutamine and putrescine were noticeably high in the susceptible rice. Coordination of different strategies in tolerant and susceptible lines show that they responded differently after exposure to salt stress. These findings can assist crop development in terms of developing tolerance mechanisms for rice crops.