Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-syndromic Oligodontia with a Novel Mutation of PAX9

Agenesis of the permanent teeth is a congenital anomaly that is frequently seen in humans. Oligodontia is a severe type of tooth agenesis involving 6 or more congenitally missing teeth, excluding the third molars. Previous studies have indicated that mutations in the homeobox gene MSX1, paired domain transcription factor PAX9, and EDA are associated with non-syndromic oligodontia. This study reports a Japanese family (eight of 14 family members affected) with non-syndromic oligodontia who preferentially lacked molar teeth. In this family, a novel frameshift mutation (321_322insG) was identified in the paired domain of PAX9. The frameshift mutation caused altered amino acids in the paired domain and premature termination of translation by 26 amino acids. When transfected into COS-7 cells, the mRNA expression of 321_322insG PAX9 was comparable with that of wild-type PAX9. However, the mRNA of 321_322insG PAX9 was more unstable than that of wild-type PAX9. This mRNA instability caused a marked decrease in protein production, as evaluated by Western blot analysis and immunostaining. These findings suggest that the 321_322insG mutation causes insufficient function of PAX9 protein and haploinsufficiency as a genetic model of familial non-syndromic oligodontia with a PAX9 mutation.
Solution structure of the cap-independent translational enhancer and ribosome-binding element in the 3′ UTR of turnip crinkle virus

The 3′ untranslated region (3′ UTR) of turnip crinkle virus (TCV) genomic RNA contains a cap-independent translation element (CITE), which includes a ribosome-binding structural element (RBSE) that participates in recruitment of the large ribosomal subunit. In addition, a large symmetric loop in the RBSE plays a key role in coordinating the incompatible processes of viral translation and replication, which require enzyme progression in opposite directions on the viral template. To understand the structural basis for the large ribosomal subunit recruitment and the intricate interplay among different parts of the molecule, we determined the global structure of the 102-nt RBSE RNA using solution NMR and small-angle x-ray scattering. This RNA has many structural features that resemble those of a tRNA in solution. The hairpins H1 and H2, linked by a 7-nucleotide linker, form the upper part of RBSE and hairpin H3 is relatively independent from the rest of the structure and is accessible to interactions. This global structure provides insights into the three-dimensional layout for ribosome binding, which may serve as a structural basis for its involvement in recruitment of the large ribosomal subunit and the switch between viral translation and replication. The experimentally determined three-dimensional structure of a functional element in the 3′ UTR of an RNA from any organism has not been previously reported. The RBSE structure represents a prototype structure of a new class of RNA structural elements involved in viral translation/replication processes.
New algorithm for simulation of proteoglycan loss and collagen degeneration in the knee joint: Data from the osteoarthritis initiative

Osteoarthritis is a harmful joint disease but prediction of disease progression is problematic. Currently, there is only one modeling framework which can be applied to predict the progression of knee osteoarthritis but it only considers degenerative changes in the collagen fibril network. Here, we have developed the framework further by considering all of the major tissue changes (proteoglycan content, fluid flow, and collagen fibril network) occurring in osteoarthritis. While excessive levels of tissue stresses controlled degeneration of the collagen fibril network, excessive levels of tissue strains controlled the decrease in proteoglycan content and the increase in permeability. We created four knee joint models with increasing degrees of complexity based on the depth‐wise composition. Models were tested for normal and abnormal, physiologically relevant, loading conditions in the knee. Finally, the predicted depth‐wise compositional changes from each model were compared against experimentally observed compositional changes in vitro. The model incorporating the typical depth‐wise composition of cartilage produced the best match with experimental observations. Consistent with earlier in vitro experiments, this model simulated the greatest proteoglycan depletion in the superficial and middle zones, while the collagen fibril degeneration was located mostly in the superficial zone. The presented algorithm can be used for predicting simultaneous collagen degeneration and proteoglycan loss during the development of knee osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1673–1683, 2018.
Organization and nucleotide sequence of a densovirus genome imply a host-dependent evolution of the parvoviruses

The genome structure of a densovirus from a silkworm was determined by sequencing more than 85% of the complete genome DNA. This is the first report of the genome organization of an insect parvovirus deduced from the DNA sequence. In the viral genome, two large open reading frames designated 1 and 2 and one smaller open reading frame designated 3 were identified. The first two open reading frames shared the same strand, while the third was found in the complementary sequence. Computer analysis suggested that open reading frame 2 may encode all four structural proteins. The genome organization and a part of the nucleotide sequence were conserved among the insect densovirus, rodent parvoviruses, and a human dependovirus. These viruses may have diverged from a common ancestor.
Should oxyhaemoglobin saturation be monitored continuously during the 6-minute walk test?

Guidelines for conducting the 6-minute walk test (6MWT) indicate that oxyhaemoglobin saturation (SpO 2) should not be monitored constantly during the test. The aim of this study was to determine whether the nadir SpO2 differs from the end-6MWT SpO2 in patients with chronic respiratory disease. A total of 86 subjects underwent the 6MWT according to a standardized protocol with continuous monitoring of SpO2 by pulse oximeter. Comparison of nadir SpO2 and end SpO2 was made and the proportion of subjects with important desaturation according to each measure was determined. The effect of resting during the 6MWT on the likelihood of a significant difference between nadir and end SpO2 was evaluated. A total of 29 subjects with chronic obstructive pulmonary disease (COPD; mean [SD] forced expiratory volume in 1 second [FEV1] 51[21] % predicted) and 57 with interstitial lung disease (ILD; TLCO 49[18] % predicted) were studied. Nadir SpO2 was slightly lower than end-test SpO2 (median 87% vs. 88%, p < 0.001) with differences ranging from 1% to 10%. Those who rested during the test (n = 14) were more likely to have a significant difference between nadir SpO2 and end SpO2 (p = 0.04). End SpO2 did not accurately identify desaturation in 21% of subjects. No differences between COPD and ILD were observed. For most patients with chronic respiratory disease, the end SpO2 and the nadir SpO 2 are similar during the 6MWT. However, the end SpO2 does not give an accurate estimate of nadir SpO2 in patients who rest. Consideration should be given to the constant monitoring of SpO2 during the 6MWT.
Returning to Stimulants in Children with Treatment Resistant ADHD: A Case Series.

Objective To present a case series of children retrialed on stimulants after initial poor stimulant responses given the paucity of information on the usefulness of this strategy. Methods Health records from an ADHD medication service were obtained for six children who: (i) were medication naïve at service entry; (ii) had trials of at least one stimulant from each stimulant class; (iii) subsequently received a non-stimulant ADHD medication; and, (iv) were then retried on stimulants. Results Initial stimulant discontinuation was a function of adverse effects and/or limited symptom improvement. Minimal response and/or adverse effects to non-stimulants contributed to the decision to retry stimulants. Final ADHD symptom ratings by parents and teachers were significantly better than baseline for this cohort. Three were discharged on stimulants, two as monotherapy. Conclusion Further study is required to develop evidence-based treatment algorithms for treatment resistant ADHD. Retrying a stimulant may be one option.
Are Close Elections Random?: Online Appendix

The model of campaigning in our paper describes a very simple model of the campaign process. In this supplement we detail a theoretically richer model that captures the continuous time decisions of political campaigns. We show that the predictions from our simple game are maintained under much more general conditions, where candidates are learning and campaigning in continuous time. Specically, we show that under the general conditions of the dierential game there is still a ood of resources into marginal elections, but that the regression discontinuity remains identied at the margin. Let there be two candidates always, each denoted by i2 f1; 2g, and let their respective vote shares (the fraction of the electorate voting for them) in an election be x and y respectively. throughout a campaign that lasts from t = 0 to the election date t = , the parties observe a continuous poll that oers vote share estimates (
Phase I and Pharmacokinetic Study of IV Vinflunine in Combination with Gemcitabine for Treatment of Advanced Non-small Cell Lung Cancer in Chemonaive Patients

Introduction: Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients. Methods: A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks. Results: Nineteen patients were included in this study. Three patients experienced a dose limiting toxicity, with constipation in one patient, hypertension in one patient, and constipation and febrile neutropenia in one patient. The combination of VFL 320 mg/m2 and gemcitabine 1250 mg/m2 was defined as the maximum tolerated dose. The recommended dose was established at the dose of VFL 320 mg/m2 combined with gemcitabine 1000 mg/m2. Neither VFL nor gemcitabine seemed to be influencing the pharmacokinetics of each other. All patients were evaluable for tumor response. Seven presented a partial response and eight experienced a stable disease. Conclusions: The combination of VFL 320 mg/m2 administered on day 1 combined with gemcitabine 1000 mg/m2 given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients.
The transient nature of the Th17 phenotype

CD4+ Th lymphocytes represent a heterogeneous population of cells that play an essential role in adaptive immunity. In addition to type 1 (Th1) and type 2 (Th2) cells, a third subset of CD4+ Th effector cells has recently been discovered, named type 17 (Th17) because of its unique ability to produce interleukin (IL)‐17. Initial studies in mice suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells are protective. Studies in humans have demonstrated the plasticity of Th17 cells and their ability to convert to Th1 cells. This Th17 to Th1 cell plasticity has also been confirmed in mice and, furthermore, it was found that Th17 cells appear to be pathogenic only when they shift to Th1 cells. A study in this issue of the European Journal of Immunology uses an IL‐17 fate mapping mouse strain, which permits the identification of the cells that have been IL‐17 producers, to provide definitive evidence that Th17 cells, either generated in vitro or in vivo, represent a transient phenotype that tend to convert into IFN‐γ‐producing cells. Our Commentary discusses this interesting point in light of previous data suggesting the same concept.
Revisiting the Force-Joint Angle Relationship After Eccentric Exercise

Abstract Welsh, MC, Allen, DL, Batliner, ME, and Byrnes, WC. Revisiting the force-joint angle relationship after eccentric exercise. J Strength Cond Res XX(X): 000–000, 2015—The purpose of this study was to evaluate force-angle curve fitting techniques pre-eccentric exercise, quantify changes in curve characteristics postexercise, and examine the relationship between curve changes and markers of muscle damage. Fourteen males unaccustomed to eccentric exercise performed 60 eccentric muscle actions of the elbow flexors. Maximal voluntary isometric force was measured throughout a range of angles pre- (Pre1 and Pre2), immediately post (IP), and 1, 2, 4, and 7 days postexercise. Force-angle curves for each visit were constructed using second-order polynomials. Changes in curve characteristics (optimal angle, peak force, curve height), range of motion, soreness, and creatine kinase activity were quantified. Optimal joint angle and force at optimal angle were significantly correlated from Pre1 to Pre2 (ICC = 0.821 and 0.979, respectively). Optimal angle was significantly right shifted (p = 0.035) by 10.4 ± 12.9° from Pre2 to IP and was restored by 1 day post exercise. Interestingly, the r 2 value for curve fit was significantly decreased (p < 0.001) from Pre2 (r 2 = 0.896) to IP (r 2 = 0.802) and 1 day post exercise (r 2 = 0.750). Curve height was significantly decreased (39%) IP and restored to pre-exercise height by 4 days postexercise. There was no correlation between optimal angle or curve height and other damage markers. In conclusion, force-angle relationships can be accurately described using second-order polynomials. After eccentric exercise, the force-angle curve is flattened and shifted (downward and rightward), but these changes are not correlated to other markers of muscle damage. Changes in the force-angle relationship are multifaceted, but determining the physiological significance of these changes requires further investigation.
ISOLATING A ROLE FOR NATURAL SELECTION IN SPECIATION: HOST ADAPTATION AND SEXUAL ISOLATION IN NEOCHLAMISUS BEBBIANAE LEAF BEETLES

Muller (1942) and Mayr (1963) hypothesized that natural selection indirectly causes the evolution of reproductive barriers between allopatric populations by causing adaptive genetic divergence that pleiotropically promotes prezygotic or postzygotic incompatibility. Under this mechanism, herbivorous insect populations should be more prone to speciate if they are adapting to different host plants, because the evolution of reproductive isolation will be accelerated above the rate promoted by genetic drift and host‐independent sources of selection alone. Although the Muller‐Mayr hypothesis is widely accepted, little direct evidence has been collected in support of selection's role in allopatric speciation. This paper offers a method for isolating and evaluating the contribution of host plant‐related natural selection pressures to the reproductive isolation between allopatric herbivore populations.
Human Neutrophils Oxidize Low-Density Lipoprotein by a Hypochlorous Acid- Dependent Mechanism: The Role of Vitamin C

Abstract Oxidatively modified lowdensity lipoprotein (LDL) has been strongly implicated in the pathogenesis of atherosclerosis. Peripheral blood leukocytes, such as neutrophils, can oxidize LDL by processes requiring superoxide and redoxactive transition metal ions; however, it is uncertain whether such catalytic metal ions are available in the artery wall. Stimulated leukocytes also produce the reactive oxidant hypochlorous acid (HOCl) via the heme enzyme myeloperoxidase. Since myeloperoxidasederived HOCl may be a physiologically relevant oxidant in atherogenesis, we investigated the mechanisms of neutrophilmediated LDL modification and its possible prevention by the antioxidant ascorbate (vitamin C). As a sensitive marker of LDL oxidation, we measured LDL thiol groups. Stimulated human neutrophils (5106 cells/ml) incubated with human LDL (0.25 mg protein/ml) timedependently oxidized LDL thiols (33% and 79% oxidized after 10 and 30 min, respectively). Supernatants from stimulated neutrophils also oxidized LDL thiols (33% oxidized after 30 min), implicating longlived oxidants such as Nchloramines. Experiments using specific enzyme inhibitors and oxidant scavengers showed that HOCl, but not hydrogen peroxide nor superoxide, plays a critical role in LDL thiol oxidation by neutrophils. Ascorbate (200 M) protected against neutrophilmediated LDL thiol oxidation for up to 15 min of incubation, after which LDL thiols became rapidly oxidized. Although stimulated neutrophils accumulated ascorbate during oxidation of LDL, preloading of neutrophils with ascorbate did not attenuate oxidant production by the cells. Thus, activated neutrophils oxidize LDL thiols by HOCl and Nchloramine dependent mechanisms and physiological concentrations of vitamin C delay this process, most likely due to scavenging of extracellular oxidants, rather than by attenuating neutrophil oxidant production.
Social Dynamics and the Future of Technology-Driven Crime

The future of cybercrime and cyber terrorism is not likely to follow some monotonic, simple deterministic path. The complex interplay of technology and social forces, as demonstrated in the previous chapters, reveals that this outcome will be anything but straightforward. However, this reality does not mean that through a better understanding of the social relationships between technology and humans, we cannot influence, at least partially, that future. In particular, social scientists have accumulated a significant body of knowledge on how various types of social processes--such as sentiment, status, social control and distributive justice, just to name a few – operate and interact to form our social world. We are now just beginning to gain a better understanding of how these processes are altered through the catalyst of digital technologies. ABSTRACT
Trehalose dihydrate from Tremella fuciformis

The title compound, C12H22O11·2H2O {systematic name: 6,6′-oxybis[2-(hydroxymethyl)-3,4,5,6-tetrahydro-2H-pyran-3,4,5-triol] dihydrate}, is a disaccharide, which was isolated from Tremella fuciformis. The molecule contains two six-membered rings, both of which adopt a chair conformation. Extensive O—H⋯O hydrogen bonds occur in the crystal structure.
Apparatus for dynamic balance training during treadmill walking.

OBJECTIVE A presentation of a novel apparatus for dynamic balance training during treadmill walking, which was tested in a case study. SUBJECT The subject was a man with incomplete chronic spinal cord injury (C5), graded D on the American Spinal Injury Association Impairment Scale. METHODS Following a 6-month baseline period, 4 weeks of control treatment (treadmill walking) and a subsequent 4 weeks of experimental treatment (treadmill walking assisted by the apparatus) were compared. Outcome measures were Lower Extremities Motor Score, Berg Balance Scale, 10-metre walking test and 9-minute walking test. RESULTS During the baseline period the changes in the outcome measures were small. After the control treatment the balance score remained unchanged, while walking speed and walking endurance increased moderately. Experimental treatment resulted in further substantial changes in balance and walking endurance scores, while further increase in walking speed was moderate. At follow-up these values were maintained. Lower Extremities Motor Scores were almost identical in all study phases. CONCLUSION The subject's walking and balancing abilities improved moderately after the control treatment, while greater improvement occurred during experimental treatment. This indicates that the apparatus developed might be an important tool for facilitating dynamic balancing training during treadmill walking.
The Effects of Class Ic Antiarrhythmics on Tetrodotoxin-Resistant Na+ Currents in Rat Sensory Neurons

IV or oral administration of antiarrhythmics has been reported to be effective for relieving neuropathic pain. Recent reports have indicated that tetrodotoxin-resistant (TTX-R) Na+ channels play important roles in the nerve conduction of nociceptive sensation. In the present study, we investigated the effects of flecainide, pilsicainide (class Ic antiarrhythmics), and lidocaine (a class Ib drug) on TTX-R Na+ currents in rat dorsal root ganglion neurons using the whole-cell patch-clamp method. Flecainide, pilsicainide, and lidocaine reversibly blocked the peak amplitude of TTX-R Na+ currents in a concentration-dependent manner with half-maximum inhibitory concentration values of 8.5 ± 6.6 μM (n = 7), 78 ± 6.9 μM (n = 7), and 73 ± 6.8 μM (n = 7), respectively. Each drug shifted the inactivation curve for the TTX-R Na+ currents in the hyperpolarizing direction and caused a use-dependent block. We also studied an interaction between these antiarrhythmics on TTX-R Na+ channels. Additional application of flecainide or pilsicainide to lidocaine resulted in an additive increase of tonic and use-dependent block. These results suggest that the inhibition of TTX-R Na+ currents of dorsal root ganglion neurons by such antiarrhythmics is attributable, at least partly, to their antinociceptive effects.
Improving the Reliability of Physician Performance Assessment: Identifying the “Physician Effect” on Quality and Creating Composite Measures

Background:The proliferation of efforts to assess physician performance underscore the need to improve the reliability of physician-level quality measures. Objective:Using diabetes care as a model, to address 2 key issues in creating reliable physician-level quality performance scores: estimating the physician effect on quality and creating composite measures. Design:Retrospective longitudinal observational study. Subjects:A national sample of physicians (n = 210) their patients with diabetes (n = 7574) participating in the National Committee on Quality Assurance-American Diabetes Association's Diabetes Provider Recognition Program. Measures:Using 11 diabetes process and intermediate outcome quality measures abstracted from the medical records of participants, we tested each measure for the magnitude of physician-level variation (the physician effect or “thumbprint”). We then combined measures with a substantial physician effect into a composite, physician-level diabetes quality score and tested its reliability. Results:We identified the lowest target values for each outcome measure for which there was a recognizable “physician thumbprint” (ie, intraclass correlation coefficient ≥0.30) to create a composite performance score. The internal consistency reliability (Cronbach's α) of the composite score, created by combining the process and outcome measures with an intraclass correlation coefficient ≥0.30, exceeded 0.80. The standard errors of the composite case-mix adjusted score were sufficiently small to discriminate those physicians scoring in the highest from those scoring in the lowest quartiles of the quality of care distribution with no overlap. Conclusions:We conclude that the aggregation of well-tested quality measures that maximize the “physician effect” into a composite measure yields reliable physician-level quality of care scores for patients with diabetes.