Miracle-dz/UniFAR-FTUs huggingface dataset:
Dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapy – focus on alogliptin

Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones. The five available DPP-4 inhibitors, also known as ‘gliptins’ (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin), are small molecules used orally with similar overall clinical efficacy and safety profiles in patients with type 2 diabetes. The main differences between the five gliptins on the market include: potency, target selectivity, oral bioavailability, long or short half-life, high or low binding to plasma proteins, metabolism, presence of active or inactive metabolites, excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug–drug interactions. On average, treatment with gliptins is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%–0.8%, with about 40% of diabetic subjects at target for the HbA1c goal <7%. There are very few studies comparing DPP-4 inhibitors. Alogliptin as monotherapy or added to metformin, pioglitazone, glibenclamide, voglibose, or insulin therapy significantly improves glycemic control compared with placebo in adult or elderly patients with inadequately controlled type 2 diabetes. In the EXAMINE trial, alogliptin is being compared with placebo on cardiovascular outcomes in approximately 5,400 patients with type 2 diabetes. In clinical studies, DPP-4 inhibitors were generally safe and well tolerated. However, there are limited data on their tolerability, due to their relatively recent marketing approval. Alogliptin will be used most when avoidance of hypoglycemic events is paramount, such as in patients with congestive heart failure, renal failure, and liver disease, and in the elderly.
Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium.

In recent years, fluorescence microscopy based on two-photon excitation has become a popular tool for biological and biomedical imaging. Among its advantages is the enhanced depth penetration permitted by fluorescence excitation with the near-infrared photons, which is particularly attractive for deep-tissue imaging. To fully utilize two-photon fluorescence microscopy as a three-dimensional research technique in biology and medicine, it is important to characterize the two-photon imaging parameters in a turbid medium. We investigated the two-photon point spread functions (PSFs) in a number of scattering samples. Gel samples containing 0.1-microm fluorescent microspheres and Liposyn III were used as phantoms mimicking the turbid environment often found in tissue. A full characterization of the two-photon PSFs of a water and oil immersion objective was completed in samples composed of 0, 0.25, 0.5, 1, and 2% Liposyn III. Our results show that up to depths of about 100 (oil) and 200 microm (water), the presence of scatterers (up to 2% Liposyn III) does not appreciably degrade the PSF widths of the objectives.
Ocean acidification influences host DNA methylation and phenotypic plasticity in environmentally susceptible corals

As climate change challenges organismal fitness by creating a phenotype–environment mismatch, phenotypic plasticity generated by epigenetic mechanisms (e.g., DNA methylation) can provide a temporal buffer for genetic adaptation. Epigenetic mechanisms may be crucial for sessile benthic marine organisms, such as reef‐building corals, where ocean acidification (OA) and warming reflect in strong negative responses. We tested the potential for scleractinian corals to exhibit phenotypic plasticity associated with a change in DNA methylation in response to OA. Clonal coral fragments of the environmentally sensitive Pocillopora damicornis and more environmentally robust Montipora capitata were exposed to fluctuating ambient pH (7.9–7.65) and low pH (7.6–7.35) conditions in common garden tanks for ~6 weeks. M. capitata responded weakly, or acclimated more quickly, to OA, with no difference in calcification, minimal separation of metabolomic profiles, and no change in DNA methylation between treatments. Conversely, P. damicornis exhibited diminished calcification at low pH, stronger separation in metabolomic profiles, and responsiveness of DNA methylation to treatment. Our data suggest corals differ in their temporal dynamics and sensitivity for environmentally triggered real‐time epigenetic reprogramming. The generation of potentially heritable plasticity via environmental induction of DNA methylation provides an avenue for assisted evolution applications in corals under rapid climate change.
Patient characteristics associated with high-risk methotrexate concentrations and toxicity.

PURPOSE Following high-dose methotrexate (HD-MTX) treatment, delayed MTX elimination is an important problem because it necessitates increased leucovorin rescue and additional hospitalization for hydration and urinary alkalinization. Our purpose was to identify factors associated with high-risk MTX plasma concentrations (defined by plasma concentration > or = 1.0 mumol/L at 42 hours from the start of MTX) and with toxicity. PATIENTS AND METHODS Variables associated with MTX concentrations and toxicity were assessed in 134 children treated with one to five courses of HD-MTX (900 to 3,700 mg/m2 intravenously [i.v.] over 24 hours for a total of 481 courses) for acute lymphoblastic leukemia (ALL). RESULTS High-risk MTX concentrations, toxicity (usually mild mucositis), and delay in resuming continuation chemotherapy occurred in 106 (22%), 123 (26%), and 66 (14%) of 481 courses, respectively. Using a mixed effects model for repeated measures, high-risk MTX concentrations were significantly associated with a higher MTX area-under-the-concentration-time curve (AUC), low urine pH, emesis, low MTX clearance, low urine output relative to intake, use of antiemetics during the MTX infusion, and concurrent intrathecal therapy (all p values < .01). Clinical toxicities and delay in resumption of continuation chemotherapy due to myelosuppression were more common in those with high 42-hour MTX concentrations, despite increased leucovorin rescue for all patients with high-risk MTX concentrations. However, with individualized rescue, no patient developed life-threatening toxicity. A more aggressive hydration and alkalinization regimen for subsequent courses reduced the frequency of high-risk MTX concentrations to 7% of courses (13 of 183) (P = .0001), and the frequency of toxicity decreased to 11% of courses (P = .0074). CONCLUSION This study identified several clinical variables that influence MTX disposition that, when modified, can reduce the frequency of high-risk MTX concentrations and toxicity.
Alterations of signaling pathways in muscle tissues of patients with amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manifests as progressive weakening of muscles. The diagnosis and prognosis of ALS are often unclear, so useful biomarkers are needed. Methods: Total proteins were extracted from muscle samples from 36 ALS, 17 spinal muscular atrophy (SMA), and 36 normal individuals. The expression levels of 134 proteins and phosphoproteins were assessed using protein pathway array analysis. Results: Seventeen proteins were differentially expressed between ALS and normal muscle, and 9 proteins were differentially expressed between ALS and SMA muscle. The low‐level expression of Akt and Factor XIIIB correlates with unfavorable survival, and the risk score calculated based on these proteins predicts the survival of each individual patient. Conclusions: Some proteins could be selected as clinically useful biomarkers. Specifically, Akt and Factor XIIIB were found to be promising biomarkers for estimating prognosis in ALS. Muscle Nerve, 2012
Avian poxvirus infection in a white-tailed sea eagle (Haliaeetus albicilla) in Japan

An adult female white-tailed sea eagle (Haliaeetus albicilla), over 12 years old, was found moribund and sent to the Wildlife Rescue Center in Kushiro, Japan. Grossly, the bird had multifocal yellow to black nodules in the beak, tongue, mucosa of the oral cavity, eyelids, and legs. Histologically, the cutaneous nodules revealed severe epidermal hyperplasia. The thickened epithelium, from prickle cell layer to horny layer, consisted of swollen keratinocytes containing frequent eosinophilic intra-cytoplasmic inclusions, Bollinger bodies. Ultrastructurally, the epidermal cells had cytoplasmic viral particles with characteristics of poxvirus. Furthermore, the 4b core gene sequence of an avian poxvirus was detected in a DNA sample prepared from the nodular lesions by polymerase chain reaction. The nucleotide sequence of the polymerase chain reaction product showed 78 to 95% similarities to the sequences of other avian poxviruses. Phylogenetic analysis showed that the sequence is clustered in clade A but distant from all the subclades previously reported. The results imply that it is a novel avian poxvirus. To our knowledge this is the first report of avian poxvirus infection in white-tailed sea eagles.
Complementary Lattice Arrays for Coded Aperture Imaging

In this work, we propose the concept of complementary lattice arrays in order to enable a broader range of designs for coded aperture imaging systems. We provide a general framework and methods that generate richer and more flexible designs compared to the existing techniques. Besides this, we review and interpret the state-of-the-art uniformly redundant array designs, broaden the related concepts, and propose new design methods.
Reframing School Dropout as a Public Health Issue

Good education predicts good health, and disparities in health and in educational achievement are closely linked. Despite these connections, public health professionals rarely make reducing the number of students who drop out of school a priority, although nearly one-third of all students in the United States and half of black, Latino, and American Indian students do not graduate from high school on time. In this article, we summarize knowledge on the health benefits of high school graduation and discuss the pathways by which graduating from high school contributes to good health. We examine strategies for reducing school dropout rates with a focus on interventions that improve school completion rates by improving students' health. Finally, we recommend actions health professionals can take to reframe the school dropout rate as a public health issue and to improve school completion rates in the United States.
[Treatment options and common problems in patients with maxillofacial trauma].

BACKGROUND The approach and type of management along with the common complications in maxillofacial trauma were evaluated in this study. METHODS Medical records of 602 patients (486 males; 116 females; mean age 28,4+/-15,2; range 1 to 80 years) with maxillofacial fractures, admitted to the Department of Otolaryngology between 1992 and 2004, were evaluated in this study. Maxillofacial fracture was diagnosed by clinical and radiological findings. Sex and age distribution of patients, etiology of trauma, localization of the fractures, treatment modalities, time to treatment after the trauma and postoperative complications were recorded. RESULTS There were 257 (42,7%) mandible, 156 (25,9%) nose, 66 (11%) maxillary, 34 (5,6%) zygoma, 32 (5,3%) multiple facial, 29 (4,8%) blow-out and 28 (4,7%) frontal sinus fractures. While 256 (43%) patients underwent closed reduction, 346 (57%) patients were treated by open reduction. Postoperative complications were seen in 8,3% (51) of patients. CONCLUSION Although associated with some complications, open reduction and miniplate fixation should be the preferred treatment option, since it provides a powerful fixation, is easy to perform, and has better esthetic and cosmetic results.
Delayed diagnosis of pulmonary tuberculosis in city hospitals.

BACKGROUND Delays in the diagnosis of tuberculosis may result in increased patient morbidity and in further spread of the disease. We examined the clinical acumen of the medical staff in the diagnosis of tuberculosis and investigated the reasons for delay in the identification and treatment of patients with pulmonary tuberculosis. METHODS A retrospective chart review was undertaken between July 1985 and June 1988 on all patients with culture-proven pulmonary tuberculosis at two inner city hospitals. Time intervals between admission and the clinical suspicion, diagnosis, and treatment of tuberculosis were determined. Clinical features were evaluated for their effect on these time intervals. RESULTS Eighty-five patients with culture-proven pulmonary tuberculosis were identified. Tuberculosis was suspected in 36 patients on admission. By the end of 1 week, tuberculosis was confirmed in 50 patients and suspected in 23 others. Twenty percent of patients either died or were discharged before the diagnosis of tuberculosis was made. Older patients (> 65 years) were misdiagnosed more commonly than younger patients (82% vs 48%). Patients without respiratory symptoms were misdiagnosed more frequently (78% vs 49%) than were those with symptoms. Other reasons for delayed diagnosis and treatment included low use of tuberculin skin tests, misinterpretation of unusual chest roentgenograms, and waiting for culture results in patients with negative acid-fast smears. CONCLUSIONS The diagnosis and treatment of patients with pulmonary tuberculosis is often delayed owing to atypical presentations and slow confirmation by culture. Improved clinical acumen, development of rapid diagnostic tests, and the institution of early empiric therapy are desirable to control this disease.
Maize and Biodiversity : The Effects of Transgenic Maize in Mexico Chapter 6 Assessment of Social and Cultural Effects Associated with Transgenic Maize Production for the Article 13 Initative on Maize and Biodiversity Prepared

Note: Ten chapters were prepared as background for the work of the Maize Advisory Group and for input to the public symposium, held 11 March 2004, in Oaxaca as part of the CEC Article 13 study on maize and biodiversity. These chapters were later reviewed and revised prior to this release, based on comments received at the symposium and during the subsequent comment period. Responses to reviewers are provided at <www.cec. org/maize/>.
Protective Effect of Ca- Folinate and Ginseng in Male Rats Treated with Methotrexate

The objective of this study was to assess the prevalence of neuron and hepatotoxicity of Methotrexate (MTX) and prophylactic response to Ca- Folinate (Ca-F) and Ginseng (G). Forty two of male albino rat were divided to seven groups six rats for each. 1 st control group received 1ml saline i.p daily for 4weeks (C), 2 nd group treated with Ca-F (5 mg /kg b.wt i.p.) for 4 weeks. 3 rd group treated with G (25 mg /kg b.wt orally) for 4 weeks. 4 th group treated with MTX (0.45 mg /kg b.wt i.p.) for 4 weeks. 5 th group treated with MTX + Ca-F (0.45 mg/kg and 5 mg/ kg i.p.) for 4 weeks, respectively. 6 th group treated with MTX + G (0.45 mg/kg and 25 mg/ kg i.p.) for 4 weeks, respectively. 7 th group treated with MTX + Ca-F + G (0.45 mg/kg, 5 mg/kg and 25 mg/ kg i.p) for 4 weeks, respectively. In this study, aspartic acid (ASP), glutamic acid (GLU), ALT, AST, γ-GT, MDA, GSSG and NO were increase (P< 0.05) in MTX group comparing with control group in rat brain. Glycine (GLY), γ amino butyric acid (GABA), Norepinephrine (NE), Dopamine (DA), serotonin (5TH) and GSH were decrease (P< 0.05) in MTX group comparing with control group in rat brain. All these parameters were improved with G, F and there combination comparing with MTX group. Histopathological examination showed ameliorates effect for all treatments against MTX pathogenesety. It could be concluded that F and G influences and regeneration of neurons amino acids and catecholamine's activity and decrease liver enzymes and oxidative stress markers.
Relationship Between Cognitive Distortions and Psychological Disorders Across Diagnostic Axes

The Relationship Between Cognitive Distortions and Psychological Disorders Across Diagnostic Axes The purpose of this study was twofold: First, the study sought to determine whether or not cognitive distortions correlated with the number and severity of psychological disorders across diagnostic axes. Second, the study endeavored to assess further the validity and reliability of a promising new self-report measure, The Inventory of Cognitive Distortions (ICD), by correlating this instrument with clinical diagnoses as determined by the Millon Clinical Multiaxial Inventory-III. The sample was selected from a heterogeneous adult outpatient population. Participants meeting inclusion criteria presented for psychological treatment or assessment. Excluded were participants who had less than an eighth grade education, or who met diagnostic criteria for a number of neurological disorders. The study was correlational in design. Results supported the reliability and validity of the ICD as an assessment instrument measuring cognitive distortions, because the ICD determined that approximately half of the variance in both the number and severity of psychological dysfunction, on both Axis I and Axis II, was accounted for by the frequency of cognitive distortions.
Software Development Practices in Open Software Development Communities: A Comparative Case Study

This study presents an initial set of findings from an empirical study of social processes, technical system configurations, organizational contexts, and interrelationships that give rise to open software. "Open software", or more narrowly, open source software, represents an approach for communities of like-minded participants to develop software system representations that are intended to be shared freely, rather than offered as closed commercial products. While there is a growing popular literature attesting to open software [DiBona, Ockman, Stone 1999], there are very few systematic empirical studies [e.g., Mockus, Fielding, Herbsleb 2000] that informs how these communities produce software. Similarly, little is known about how people in these communities coordinate software development across different settings, or about what software processes, work practices, and organizational contexts are necessary to their success. To the extent that academic research communities and commercial enterprises seek the supposed efficacy of open software [Smarr and Graham 2000], they will need grounded models of the processes and practices of open software development to allow effective investment of their resources. This study investigates four communities engaged in open software development. Case study methods are used to compare practices across communities.
Accounting as story telling: Merchant activities and commercial relations in eighteenth century France

Purpose - The purpose of this paper is to extend to accounting and accounting texts the arguments of Phillips which suggest that organisational analysis can be enriched by a greater interface with narrative fiction as a means to bring organisations to life. The paper also introduces the work of Bottin which argues that accounting manuals can be considered as source documents for economic history, more than simply being of purely pedagogical value. Both approaches inform the research into the specialised accounting manual, the Design/methodology/approach - This paper uses archival-based historical methods to examine the Findings - In his manual, Gaignat recreates merchant activities and commercial relations of eighteenth century France. Gaignat does not content himself with re-copying material at his disposal or with creating fictitious examples. Rather, through his in-depth development of case studies and examples of actual accounting methods, he offers the reader insights into the strategic nature of the social and economic milieu in which commercial success might be achieved. Practical implications - The research approach is transferable to other settings, motivating renewed interest in the history of accounting literature. The stories related in the Originality/value - The research method is original in that the methodological approach is new to accounting history, but part of a debate within history more generally.
microRNA/microRNA* complementarity is important for the regulation pattern of NFYA5 by miR169 under dehydration shock in Arabidopsis

MicroRNAs regulate gene expression at the mRNA and translational levels. Although our previous research showed that expression of miR169 and one of its targets, NFYA5, is down- and up-regulated by drought stress, respectively, the current study shows that expression of both miR169 and NFYA5 are induced by dehydration shock. Unlike overexpression of MIR169a/b, overexpression of MIR169i/l did not decrease NFYA5 transcripts but increased NFYA5 protein levels. NFYA5 protein abundance also increased in mir169a knock-out mutants and 35S::MIR169l mir169a double mutants. When bulge #11 and bulge #16 in the miR169/miR169* duplex were mutated, both NFYA5 transcripts and the corresponding protein levels were lower in 35S::MIR169l*-mut transgenic plants than in wild-type (WT) plants, and the 35S::MIR169l*-mut transgenic plants were as sensitive to drought stress as the 35S::MIR169a plants. The mRNA and protein levels of NFYA5 did not differ substantially between WT and 35S::MIR169a*-mut transgenic plants when the two bulges were introduced in the miR169a/miR169a* duplex. Both bulge #11 and bulge #16 in the miR169/miR169* duplex were essential for different regulation patterns of NFYA5 by miR169a and miR169l. These results increase the understanding of regulatory specialization in one MIR family, and also increase our understanding of the importance of microRNA/microRNA* secondary structure.
Childhood Correlates of Blood Lead Levels in Mumbai and Delhi

Background Lead exposure has previously been associated with intellectual impairment in children in a number of international studies. In India, it has been reported that nearly half of the children have elevated blood lead levels (BLLs). However, little is known about risk factors for these elevated BLLs. Methods We conducted a retrospective cross-sectional analysis of data from the Indian National Family Health Survey, a population-based study conducted in 1998–1999. We assessed potential correlates of BLLs in 1,081 children who were < 3 years of age and living in Mumbai or Delhi, India. We examined factors such as age, sex, religion, caste, mother’s education, standard of living, breast-feeding, and weight/height percentile. Results Most children (76%) had BLLs between 5 and 20 μg/dL. Age, standard of living, weight/height percentile, and total number of children ever born to the mother were significantly associated with BLLs (log transformed) in multivariate regression models. Compared with children ≤3 months of age, children 4–11 and 12–23 month of age had 84 and 146% higher BLLs, respectively (p < 0.001). A low standard of living correlated with a 32.3% increase in BLLs (p = 0.02). Children greater than the 95th percentile for their weight/height had 31% (p = 0.03) higher BLLs compared with those who were below the 5th percentile for their weight/height. Conclusions Our study found various factors correlated with elevated BLLs in children. The correlation between greater than the 95th percentile weight/height and higher BLL may reflect an impact of lead exposure on body habitus. Our study may help in targeting susceptible populations and identifying correctable factors for elevated BLLs in Mumbai and Delhi.