Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormal WNT5A Signaling Causes Mandibular Hypoplasia in Robinow Syndrome

The study of rare genetic diseases provides valuable insights into human gene function. Here, we investigate dominant Robinow syndrome (RS), which affects the WNT5A signaling pathway. Autosomal dominant RS is caused by missense mutations in WNT5A or nonsense mutations in the adaptor protein DVL1 or DVL3. The recessive form of the disease is caused by loss-of-function mutations in the receptor ROR2. RS is characterized by hypertelorism, midface, and mandibular hypoplasia. Here, we focus on the missense mutations in WNT5A, since the impact on function is difficult to predict from in silico analysis. We used chicken embryo to express wild-type or 2 mutant versions of human WNT5A in the mandible and then examined the morphologic, cellular, and molecular effects. The 3 experimental viruses—wtWNT5A, WNT5AC83S, or WNT5AC182R—all caused shortening of the mandible on the injected side as compared with GFP controls. Although the phenotypes initially appeared similar, we uncovered specific disruption of chondrocyte polarity and shape, inhibition of cell migration, differences in target gene expression, and absence of JNK signaling only in the presence of mutant viruses. In addition, the missense mutations do not appear to block receptor binding, since in paracrine experiments, the mutant protein inhibits cell migration. In this study, we ruled out a straightforward gain or loss of function caused by the WNT5A missense mutations. Instead, the mutations are likely redirecting WNT signaling away from JNK-PCP toward other noncanonical pathways. We conclude that in RS, WNT5A missense mutations have dominant neomorphic effects that interfere with the function of the wild-type protein.
A novel diagnostic tool for detecting functional patency of the small bowel: the Given patency capsule.

BACKGROUND AND STUDY AIMS The current visualization of small-bowel strictures using traditional radiological methods is associated with high radiation doses and false-negative results. These methods do not always reveal small-bowel patency for solids. The aim is to assess the safety of the Given patency system and its ability to detect intestinal strictures in patients with strictures that are known or suspected radiologically. MATERIALS AND METHODS The Given patency capsule is composed of lactose, remains intact in the gastrointestinal tract for 40-100 hours post ingestion, and disintegrates thereafter. A total of 34 patients with small-bowel stricture were prospectively enrolled; 30 had a previous diagnosis of Crohn's disease, three had adhesion syndrome and in one ischemic enteritis was suspected. Of the patients, 15 (44.1 %) had previously undergone surgery. Following ingestion, the capsule was monitored for integrity and transit time, using a specially designed Given scanner and also radiologically. Seventeen patients had been enrolled with the intent of using the patency capsule as a preliminary test in patients with small-bowel strictures before undergoing video capsule endoscopy. RESULTS 30 patients (88.2 %) retrieved the capsule in the stool; it was intact in 20 (median transit time 22 hours), and disintegrated in 10 patients (median transit time 53 hours). Six patients complained of abdominal pain which disappeared within 24 hours. The scanner successfully indicated the presence of the capsule in 94 % of cases. Ten patients underwent video capsule endoscopy following the patency capsule examination; in all of these the video capsule passed through the small-bowel stricture. CONCLUSIONS This feasibility study has shown that the Given patency capsule is a safe, effective, and convenient tool for assessment of functional patency of the small bowel. It can indicate functional patency even in cases where traditional radiology indicates stricture.
Vowel length as evidence for a distinction between free and bound prefixes in Czech

This paper argues that Czech verbal prefixes alternate between two states, roughly corresponding to the traditional notions ‘free’ and ‘bound’. The distinction, however, is not reflected in the separability of the prefix and the verb; it is reflected in vowel length. Main evidence for the claim is drawn from the way vowel length of adpositions is treated Czech internally and from a comparison to Norwegian. Theoretically, we implement the alternation as a phrasal movement of the prefix from a VP internal position (where the prefix behaves as bound) to a VP external position, drawing on Taraldsen’s (2000) proposal for Norwegian and Svenonius’s (2004b) account of prefixation in Slavic.
Crotaline Fab antivenom for the treatment of children with rattlesnake envenomation.

OBJECTIVE There is little data regarding safety or efficacy of Crotalinae polyvalent immune Fab (ovine) antivenom (crotaline Fab) in pediatric patients. Our objective was to provide the first information regarding safety and effectiveness of this new drug in children. METHODS Data were collected prospectively and retrospectively for all consecutive pediatric patients bitten by rattlesnakes and treated at 2 urban hospitals during 2001. Cases were included if there were signs of envenomation at presentation, patient age was 13 years or less, and there was administration of crotaline Fab. Cases were excluded if antivenin (Crotalidae) polyvalent (equine origin, the conventional antivenom) was given. Primary outcome variables were snakebite severity scores throughout the course of therapy, number of vials of crotaline Fab administered, occurrence of allergic reactions, adjunct surgical therapy, and the presence of permanent sequelae or serum sickness identified at follow-up. RESULTS In the 12 cases studied, ages ranged from 14 months to 13 years (mean: 6.9; standard deviation: 4.2). Presentation snakebite severity scores ranged from 2 to 9 (mean: 5.3; standard deviation: 2.3). Total crotaline Fab doses ranged from 4 to 22 vials (mean: 12.7; standard deviation: 5.4). Initial control of symptoms was achieved with 4 to 16 vials (mean: 7.7; standard deviation: 3.7), and severity scores stabilized or improved within 24 hours in all patients. Recurrence of local swelling occurred in 1 case despite scheduled repeat doses of antivenom. No cases required surgical intervention, and no permanent sequelae were identified. No immediate or delayed hypersensitivity reactions occurred. CONCLUSION In this group of pediatric patients treated for rattlesnake envenomation, crotaline Fab antivenom was safe and seemed to be effective.
Cerebral tissue oxygenation index in very premature infants

Aim: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. Methods: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were Pao2, Paco2, pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. Results: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, Pao2, Paco2, and haemoglobin concentration. Conclusion: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time.
An area-efficient capacitively-coupled sensor readout circuit with current-splitting OTA and FIR-DAC

An area-efficient CTDSM for sensor applications is presented. The proposed capacitively-coupled CTDSM combines the functions of precision amplifier and DSM to achieve hardware efficiency. The 1-bit quantizer with FIR-DAC improves the linearity without using DEM in multi-bit architectures or large-size analog filters. The proposed currentsplitting OTA saves the capacitor area in the first integrator stage. Fabricated in a 0.18-μm CMOS, this chip draws 70 μA (? ) from a 1.8-V supply, and achieves 12-bit resolution under 2-kHz bandwidth at ±40-mV input range. The circuit area is only 0.2 mm2.
The release of potassium ions from Candida albicans in the presence of polyene antibiotics.

The addition of amphotericin methyl ester (AME) to suspensions of Candida albicans is followed by a progressively increasing rate of release of K+ from within the cell. The time taken for a given rate of release to be reached depends upon the AME concentration (the product of AME concentration and time being approximately constant), the pH and concentration of buffer, the temperature, the suspension density, and the phase of growth of the organisms. The sensitivity of C. albicans to AME decreases during the growth of a batch culture, rapid decrease occurring after the organisms have reached the stationary phase of growth. The induction of K- release does not occur at 0 °C and shows a high temperature coefficient over the range 15 to 30 °C. Suspensions of mouse LS cells are 10 to 30 times less sensitive than Candida albicans towards AME, amphotericin B and nystatin; the two types of cell display little difference in sensitivity towards perimycin and candicidin, while mouse LS cells are more sensitive than C. albicans towards filipin. Addition of sterols at the same time as AME increases the time taken for the release of K+ to reach a given rate; of the sterols tested, zymosterol was the most effective in antagonizing AME, while ergosterol was approximately twice as effective as cholesterol on a molar basis. When organisms were exposed to AME for a short time, removed and resuspended in the absence of drug, the rate of K+ release continued to increase; this increase was prevented by ergosterol: 2 x 10-5 M-ergosterol prevented further damage after organisms had been exposed to 10-6 M AME.
1 Strong Ground Motion Estimation

At the time of its founding, only a few months after the great 1906 M 7.7 San Francisco Earthquake, the Seismological Society of America noted in their timeless statement of purpose “that earthquakes are dangerous chiefly because we do not take adequate precautions against their effects, whereas it is possible to insure ourselves against damage by proper studies of their geographic distribution, historical sequence, activities, and effects on buildings. ” Seismic source characterization, strong ground motion recordings of past earthquakes, and physical understanding of the radiation and propagation of seismic waves from earthquakes provide the basis to estimate strong ground motions to support engineering analyses and design to reduce risks to life, property, and economic health associated with earthquakes. When a building is subjected to ground shaking from an earthquake, elastic waves travel through the structure and the building begins to vibrate at various frequencies characteristic of the stiffness and shape of the building. Earthquakes generate ground motions over a wide range of frequencies, from static displacements to tens of cycles per second [Hertz (Hz)]. Most structures have resonant vibration frequencies in the 0.1 Hz to 10 Hz range. A structure is most sensitive to ground motions with frequencies near its natural resonant frequency. Damage to a building thus depends on its properties and the character of the earthquake ground motions, such as peak acceleration and velocity, duration, frequency content, kinetic energy, phasing, and spatial coherence. Strong ground motion estimation must provide estimates of all these ground motion parameters as well as realistic ground motion time histories needed for nonlinear dynamic analysis of structures to engineer earthquake-resistant buildings and critical structures, such as dams, bridges, and lifelines. Strong ground motion estimation is a relatively new science. Virtually every M > 6 earthquake in the past 35 years that provided new strong ground motion recordings produced a paradigm shift in strong motion seismology. The 1979 M 6.9 Imperial Valley, California, earthquake showed that rupture velocities could exceed shear-wave velocities over a significant portion of a fault, and produced a peak vertical acceleration > 1.5 g (Spudich and Cranswick, 1984; Archuleta; 1984). The 1983 M 6.5 Coalinga, California, earthquake revealed a new class of seismic sources, blind thrust faults (Stein and Ekström,
Political Uncertainty, Financial Crisis and Market Volatility

"This paper examines the impact of political uncertainty on financial crises using a panel of 22 emerging markets. By examining political election cycles, we find that eight out of nine of the financial crises happened during the periods of political election and transition. Using a combination of probit and switching regression analysis, we find that there is a significant relationship between political election and financial crisis after controlling for differences in economic and financial conditions. We observe increased market volatility during political election and transition periods. Our results suggest that political uncertainty could be a major contributing factor to financial crisis. Thus, politics does matter in emerging markets. Since the odds of financial crisis tend to be much larger during the political election periods, institutional investors should take that into account when making emerging market investment during those time periods". Copyright Blackwell Publishers Ltd, 2004.
Transitions in Caregiving: Evaluating a Person-Centered Approach to Supporting Family Caregivers in the Community

Caregivers of older adults provide a wide range of informal supports and services that enable older adults to continue living in the community. This study describes the use of a multicomponent intervention combined with a person-centered approach to assist caregivers of older adults in the community. Four hundred and eighteen caregiver and care recipient dyads participated in this study and their outcomes related to burden, depression, well-being, and care recipient functional status were evaluated. The findings suggest that adult child and spousal caregivers experience burden differently. Programs designed to support caregivers must tailor services to the unique needs of adult child and spousal caregivers.
The role of ion cyclotron motion at Ganymede: Magnetic field morphology and magnetospheric dynamics

Ion cyclotron motion can play a role in shaping magnetospheres and governing magnetospheric dynamics, particularly in weakly magnetized systems such as the moons of outer planets. However, MHD explicitly neglects such effects. We demonstrate the importance of ion cyclotron motion in the near space environment of Ganymede using 3‐dimensional multi‐fluid simulations to account for Galileo magnetometer data from several flybys through various regions of Ganymede's magnetosphere. These simulations track several ion species and incorporate ion cyclotron effects through a comprehensive treatment of the plasma dynamics and the generalized Ohm's law equation. In the ideal MHD limit of the multi‐fluid formulation the size of Ganymede's magnetosphere is underestimated, while in the full multi‐fluid treatment the magnetosphere is shown to be in good agreement with magnetometer measurements from Galileo. The importance of treating the ion cyclotron motion is most noticeable near the magnetopause where magnetic field strengths approach zero.
Characterization of anatomic communications between the femoropatellar joint and lateral and medial femorotibial joints in cattle, using intra-articular latex, positive contrast arthrography, and fluoroscopy.

OBJECTIVE To evaluate the frequency of communication between the lateral and medial femorotibial joints and the femoropatellar joint in cattle. DESIGN 1 of 3 injection sites was randomly assigned to each ox. ANIMALS 102 limbs were obtained from 55 fresh bovine cadavers presented for necropsy with problems unrelated to the stifle. PROCEDURE The joints were injected with a mixture of latex and barium sulfate. Communication between 2 or more joints was determined by the presence of latex and contrast material in a joint adjacent to the injected joint by examining frozen sections and positive-contrast arthrography. RESULTS Communication between the 3 joints was present in 58 (56.9%) limbs. The femoropatellar and the medial femorotibial joints always communicated. Thirteen of 38 (34.2%) specimens injected in the lateral femorotibial joint did not communicate with the 2 other joints. The femoropatellar joint communicated with the lateral and medial femorotibial joints on the distal abaxial aspect of the trochlear ridge. CONCLUSION Individual anatomic variation of the stifle in cattle should be considered when diagnostic or treatment protocols are established. CLINICAL RELEVANCE The lateral femorotibial joint should be treated separately because it does not consistently communicate with the femoropatellar or medial femorotibial joint.
Temporal and Pharmacological Characterization of Angiostatin Release and Generation by Human Platelets: Implications for Endothelial Cell Migration

Platelets play an important role in thrombosis and in neo-vascularisation as they release and produce factors that both promote and suppress angiogenesis. Amongst these factors is the angiogenesis inhibitor angiostatin, which is released during thrombus formation. The impact of anti-thrombotic agents and the kinetics of platelet angiostatin release are unknown. Hence, our objectives were to characterize platelet angiostatin release temporally and pharmacologically and to determine how angiostatin release influences endothelial cell migration, an early stage of angiogenesis. We hypothesized anti-platelet agents would suppress angiostatin release but not generation by platelets. Human platelets were aggregated and temporal angiostatin release was compared to vascular endothelial growth factor (VEGF). Immuno-gold electron microscopy and immunofluorescence microscopy identified α-granules as storage organelles of platelet angiostatin. Acetylsalicylic acid, MRS2395, GPIIb/IIIa blocking peptide, and aprotinin were used to characterize platelet angiostatin release and generation. An endothelial cell migration assay was performed under hypoxic conditions to determine the effects of pharmacological platelet and angiostatin inhibition. Compared to VEGF, angiostatin generation and release from α-granules occurred later temporally during platelet aggregation. Consequently, collagen-activated platelet releasates stimulated endothelial cell migration more potently than maximally-aggregated platelets. Platelet inhibitors prostacyclin, S-nitroso-glutathione, acetylsalicylic acid, and GPIIb/IIIa blocking peptide, but not a P2Y12 inhibitor, suppressed angiostatin release but not generation. Suppression of angiostatin generation in the presence of acetylsalicylic acid enhanced platelet-stimulated endothelial migration. Hence, the temporal and pharmacological modulation of platelet angiostatin release may have significant consequences for neo-vascularization following thrombus formation.
Autonomy and reactions to health-risk information

It has been suggested that autonomy promotes enhanced reflection on novel information and reduces defensive or biased information processing. This study investigated how autonomy affected people's reactions to known versus novel health-risk information in relation to three behaviours: sun exposure, alcohol consumption and salt intake. Participants (N = 321) completed a measure of autonomy, read either known or novel health-risk information and reported their relative autonomous motivation, attitudes, perceived behavioural control, subjective norm and intentions towards reducing the health-risk behaviour concerned. In line with our hypotheses, the results showed that higher autonomy participants reported greater relative autonomous motivation towards reducing health-risk behaviours than did lower autonomy participants; this effect was mediated by perceptions of the information as less freedom-threatening. The expected interaction between Autonomy and Information Type was not observed. The results indicate that autonomy is associated with greater relative autonomous motivation to engage in health behaviours, and that autonomous motivation may subsequently influence intentions to reduce health-risk behaviour following exposure to health-risk information.
Inhibition of Mitochondrial Permeability Transition Enhances Isoflurane-Induced Cardioprotection During Early Reperfusion: The Role of Mitochondrial KATP Channels

Inhibition of the mitochondrial permeability transition pore (mPTP) mediates the protective effects of brief, repetitive ischemic episodes during early reperfusion after prolonged coronary artery occlusion. Brief exposure to isoflurane immediately before and during early reperfusion also produces cardioprotection, but whether mPTP is involved in this beneficial effect is unknown. We tested the hypothesis that mPTP mediates isoflurane-induced postconditioning and also examined the role of mitochondrial KATP (mKATP) channels in this process. Rabbits (n = 102) subjected to a 30-min coronary occlusion followed by 3 h reperfusion received 0.9% saline (control), isoflurane (0.5 or 1.0 MAC) administered for 3 min before and 2 min after reperfusion, or the mPTP inhibitor cyclosporin A (CsA, 5 or 10 mg/kg) in the presence or absence of the mPTP opener atractyloside (5 mg/kg) or the selective mKATP channel antagonist 5-hydroxydecanoate (5-HD; 10 mg/kg). Other rabbits received 0.5 MAC isoflurane plus 5 mg/kg CsA in the presence and absence of atractyloside or 5-HD. Isoflurane (1.0 but not 0.5 MAC) and CsA (10 but not 5 mg/kg) reduced (P < 0.05) infarct size (21% ± 4%, 44% ± 6%, 24% ± 3%, and 43% ± 6%, respectively, mean ± sd of left ventricular area at risk; triphenyltetrazolium staining) as compared with control (42% ± 7%). Isoflurane (0.5 MAC) plus CsA (5 mg/kg) was also protective (27% ± 4%). Neither atractyloside nor 5-HD alone affected infarct size, but these drugs abolished protection by 1.0 MAC isoflurane, 10 mg/kg CsA, and 0.5 MAC isoflurane plus 5 mg/kg CsA. The results indicate that mPTP inhibition enhances, whereas opening abolishes, isoflurane-induced postconditioning. This isoflurane-induced inhibition of mitochondrial permeability transition is dependent on activation of mitochondrial KATP channels in vivo.
Improving outcomes for patients with medication‐resistant anxiety: effects of collaborative care with cognitive behavioral therapy

Many patients with anxiety disorders remain symptomatic after receiving evidence‐based treatment, yet research on treatment‐resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication‐resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial.
Guidelines Management of stable angina pectoris Recommendations of the Task Force of the European Society of Cardiology

Stable angina pectoris is a common and disabling disorder. In recent years, its pathophysiology has been clarified and there have been major advances in its diagnosis and management. There is, however, no consensus as to the optimal strategy of investigation and treatment. Furthermore, its therapy has not been subjected to the same scrutiny by large randomized trials as has, for example, that of myocardial infarction and unstable angina. Thus, although much has been achieved in comparing the symptomatic benefit of different modalities of treatment, there is a relative paucity of information about their prognostic effects. The Task Force has therefore obtained opinions from a wide variety of experts and has tried to achieve agreement on the best contemporary approaches to the care of stable angina pectoris, bearing in mind not only the efficacy and safety of treatments, but also the availability of resources and the cost.