Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis

Objective:Immunohistochemical staining for p53 suppressor gene mutations is sensitive and, therefore, has potential for use as a complementary test for dysplasia to improve ulcerative colitis (UC) cancer surveillance program performance.Methods:A cohort of 95 patients with long standing pan-UC enrolled in a surveillance program was studied. Archival colonic biopsy specimens were stained for p53 mutations and clinical information was obtained from medical records.Results:The 37 patients who developed p53 mutations were significantly more likely to develop dysplasia or cancer (relative risk [RR] 4.53, 95% confidence interval [Cl] 2.16–9.48). The p53 mutations developed approximately 8 months before low grade dysplasia, 26 months before high grade dysplasia, and 38 months before cancer. Three of seven cancer patients with p53 mutations had Dukes’ stage C or D, whereas only one of five cancer patients without p53 mutations had Dukes’ C or D; all three patients who died from metastatic cancer had p53 mutations (three of 37 vs 0 of 58, p < 0.03). Folic acid supplementation had a small, significant protective effect for p53 mutations (RR 0.97, Cl 0.94–1.00). Conclusion:p53 Mutations 1) are associated with, and likely precede, dysplasia and cancer, 2) are associated with cancer-related mortality, and 3) may possibly be prevented by folic acid supplementation.
Probenecid enhances central nervous system uptake of 2',3'-dideoxyinosine by inhibiting cerebrospinal fluid efflux.

The effects of probenecid on the pharmacokinetics of 2',3'-dideoxyinosine (ddl) and on the distribution of ddl to cerebrospinal fluid (CSF) and brain tissue were determined in rats during and after a 2-hr i.v. infusion of ddl, 125 mg/kg/hr. Probenecid-treated rats received a loading dose of probenecid followed by an i.v. infusion of probenecid initiated 1 hr before and continued during and for 2 hr after termination of the ddl infusion. Plasma concentrations of probenecid averaged 221 +/- 34 micrograms/ml upon termination of the ddl infusion and 258 +/- 34 micrograms/ml (mean +/- S.D., n = 4) 1 hr later. In the probenecid-treated animals, ddl concentrations were higher in plasma (1.5-fold), brain (1.5-fold) and CSF (5.4-fold) at the termination of the ddl infusion and postinfusion concentrations declined more slowly compared to controls. Postinfusion, the CSF/plasma and brain/plasma ratios steadily increased to a greater extent in the probenecid-treated rats compared to control animals. The time course of plasma, CSF and brain tissue concentrations were analyzed by nonlinear least-squares regression using two different compartmental models, one which neglected the direct exchange of drug between the CSF and brain parenchyma, whereas the other allowed for such exchange to occur and neglected direct vascular transfer of drug to brain tissue. Allowing exchange between the CSF and brain tissue gave slightly improved fitting of the data from both probenecid-treated and control rats. (ABSTRACT TRUNCATED AT 250 WORDS)
Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive increase in pulmonary vascular resistance, ultimately leading to right heart failure and death. Throughout the past 20 years, numerous specific pharmacologic agents, including phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostaglandins, and more recently, soluble guanylate cyclase stimulators and selective IP prostacyclin receptor agonist, have emerged for the treatment of PAH. Early clinical trials were typically of short-term duration, comparing the effects of PAH-targeted therapies versus placebo and using exercise tolerance as the primary endpoint in most trials. A meta-analysis of these trials documented a reduction in short-term mortality of ∼40% with monotherapy. More recently, we have witnessed a progressive shift in PAH study designs using longer event-driven trials comparing the effects of upfront and sequential combination therapy on clinical worsening that is perceived as a more clinically relevant outcome measure. Recent meta-analyses also documented that combination therapy significantly reduced the risk of clinical worsening by ∼35% compared with monotherapy alone. In this review article, we will discuss the evolution of treatments and clinical trial design in the field of PAH over the past decades with a special focus on combination therapy and its current role in the management of PAH. We will also detail unresolved questions regarding the future of PAH patients’ care and the challenges of future clinical trials.
Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity

The orbitofrontal cortex seems to play a crucial role in reward‐guided learning and decision making, especially for impulsive choice procedures including delayed reward discounting. The central serotonergic system is closely involved in the regulation of impulsivity, but how the serotonergic firing rate and release, best investigated by the loudness dependence of auditory evoked potentials (LDAEP), interact with orbitofrontal activity is still unknown.
Dietary selenate versus selenite for cattle, sheep, and horses.

Food and Drug Administration regulations currently permit addition of . 3 mg of Se per kilogram of diet for chickens, turkeys, ducks, swine, sheep, and cattle. However, field reports indicate that this level may not be adequate for ruminants in all situations. Because sodium selenite is the most common supplemental form and is known to be readily absorbed to particles or reduced to insoluble elemental Se or selenides in acid, anaerobic environments, studies were conducted with dairy cattle, sheep, and horses fed sodium selenate to determine whether Se from this source was more bioavailable than Se from sodium selenite. A 2-wk period of no Se supplementation was followed by 49 or 56 d of Se supplementation at . 3 mg/kg of dietary DM. Serum Se concentrations and glutathione peroxidase (GSHPx) activities measured initially and periodically thereafter revealed no difference between Se forms in sheep and horses and only a small (P less than .05) advantage for selenate in supporting serum Se concentration in dairy cattle. Selenium concentrations in skeletal muscle and liver of sheep were not different between Se forms. Serum Se, but not GSHPx, increased with time, and . 3 mg of supplemental Se per kilogram of dietary DM from either sodium selenate or sodium selenite supported normal serum Se concentrations in sheep, dairy cattle, and horses.
Regulatory own goals: the unintended consequences of economic regulation in professional football

ABSTRACT Research question In 2010, the governing body of European football, UEFA, approved ‘Financial Fair Play’ regulations. Designed to encourage financial discipline, promote stability and foster competitive balance, they focus on a financial breakeven constraint. We analyse the impact of such constraints on the joint sporting and financial efficiency of English football clubs. Research methods The simultaneous production of both sporting and financial outputs are modelled using stochastic, non-parametric efficiency analysis. The sample is an unbalanced panel representing 60 clubs spanning the 2003/2004 to 2016/2017 seasons. Results and findings The Financial Fair Play breakeven regulation reduces average club efficiency, raises the relative importance of financial goals (capturing revenue share) whilst lowering the relative importance of sporting goals (capturing point share). The efficiency costs of regulation are not borne equally by clubs. Implications Breakeven regulations reduce the joint sporting and financial efficiency of regulated clubs, with the efficiency loss positively related to the severity of the breakeven constraint. The Financial Fair Play regulations further entrench the financial and sporting power of elite clubs and potentially undermine league competitive intensity by shifting the relative focus of clubs away from sporting productivity toward financial productivity.
Estimating the burden of 'weighing less': A systematic review and meta-analysis of low birth-weight in India.

BACKGROUND The National Family Health Survey-3 (NFHS- 3; 2005-06) reports that the prevalence of low birth-weight babies is 22% in India. This old figure is probably an underestimate as this nationwide survey acquired information on birth-weight of only 34% of babies. We aimed to make a fresh estimate of the proportion of low birth-weight babies. METHODS A systematic search was done through PubMed, Google Scholar, Cochrane Library, Medline, IndMed, Embase, WHO and Biomed Central databases. Studies published from 2004 to 2014 were included. Study quality was assessed using the adapted Mirza and Jenkins checklist. An 'adjustment' of 24% was applied to the published estimates where data were collected through records or through a combination of records and anthropometry. The adjustment was done to account for the heaping of birth-weight data at 2500 g. Metaanalysis using both random and fixed effects model was done to derive an estimate. RESULTS Nineteen studies with 44 133 subjects were included in the review. The pooled estimate for the prevalence of low birth-weight was 27% (95% CI 24%-30%) and the 'adjusted' pooled prevalence was 31% (95% CI 28%-33%). The prevalence in urban and rural areas was 30% (95% CI 23%- 38%) and 26% (95% CI 22%-30%), respectively. Regionwise estimates revealed that the prevalence at 33% was comparatively higher in eastern regions (95% CI 29%-37%). CONCLUSION The pooled prevalence of low birth-weight is higher than that reported by NFHS-3. Updated estimates should be used to guide future interventions and policies.
Functional‐adaptive anatomy of the axial skeleton of some extant marsupials and the paleobiology of the paleocene marsupials mayulestes ferox and pucadelphys andinus

In this study, the axial skeletons of two Early Paleocene marsupials, Mayulestes ferox and Pucadelphys andinus, were analyzed functionally and compared to that of six South American and three Australian species of extant marsupials. In the case of the South American opossums, myological data of the epaxial musculature were collected and analyzed and osteological‐myological associations were related to locomotor behavior. Various features of the vertebral column that relate to diet or to locomotor or postural patterns were pointed out. These features include: the craniocaudal development of the neural process of the axis; the position of the anticlinal vertebra; the morphology of the neural processes of the thoracolumbar vertebrae (orientation, length, and craniocaudal width); the length, orientation, and curvature of the transverse processes of the lumbar vertebrae; and the length and robustness of the caudal vertebrae. In both fossil forms the vertebral column is mobile and allows a great range of flexion and extension of the spine, more so than in most of the living didelphids. It is emphasized here that the analysis of the axial skeleton complements and improves the conclusions provided by the forelimb and hindlimb analyses. It is proposed that Mayulestes and Pucadelphys represent an ancestral morphotype suggesting that the generalized type of locomotion of Paleocene marsupials was partly terrestrial with some climbing ability. J. Morphol. 255:279–300, 2003. © 2003 Wiley‐Liss, Inc.
Usefulness of platelet‐derived growth factor as a prognostic factor in pulmonary adenocarcinoma

Platelet‐derived growth factor (PDGF) in the resected pulmonary adenocarcinoma tissue of 88 patients was detected immunohistochemically by the avidin‐biotin‐peroxidase technique to determine whether or not it is a prognostic parameter. The 88 patients were divided into PDGF (‐) and PDGF (+) groups according to the stainability of the factor. The PDGF (‐) group included 39 patients and the PDGF (+) group 49. The 5‐year survival rate was 53% for the PDGF (‐) group and 17% for the PDGF (+) group (P < 0.01). These findings indicate that the stainability of PDGF can be a prognostic parameter for pulmonary adenocarcinoma. © 1995 Wiley‐Liss, Inc.
The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth

Aims: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity. Population: Of 308 surviving children born at ⩽25 weeks gestation in the United Kingdom and Ireland from March to December 1995, 283 (92%) were evaluated at 30 months of age corrected for prematurity. Methods: Cerebral palsy, severe motor disability, and Bayley scores were used as dependent variables in sequential multiple regression analyses to identify factors associated with adverse outcomes. Results: Adverse outcomes were consistently more common in boys. Factors related to perinatal illness, ultrasound evidence of brain injury, and treatment (particularly postnatal steroids) were associated with adverse motor outcomes (cerebral palsy, disability or Bayley psychomotor development index). Increasing duration of postnatal steroid treatment was associated with poor motor outcomes. A score was developed for severe motor disability with good negative predictive value. In contrast, mental development was associated with a broader range of factors: ethnic group, maternal educational level, the use of antenatal steroids, and prolonged rupture of membranes in addition to chronic lung disease. Conclusion: Male sex is a pervasive risk factor for poor outcome at extremely low gestations. Avoidable or effective treatment factors are identified, which may indicate the potential for improving outcome.
Length Change Behavior of Virtual Medial Patellofemoral Ligament Fibers During In Vivo Knee Flexion

Background: In vivo length change behavior of native medial patellofemoral ligament (MPFL) fibers throughout the range of knee motion has not been reported in vivo. Purpose: To measure the length changes of various fibers of the MPFL and to determine their length change patterns during in vivo passive knee flexion. Study Design: Descriptive laboratory study. Methods: The right knees of 11 living subjects were scanned with a high-resolution computed tomography scanner at 0°, 30°, 60°, 90°, and 120° of knee flexion, and 3-dimensional (3D) models were constructed using customized software. Five patellar points were determined: 20% (point 20), 30% (point 30), 40% (point 40), 50% (point 50), and 60% (point 60) from the superior pole of the patella. The Schöttle femoral point (point F) was marked on a translucent 3D model of a true lateral view. Five virtual fibers connecting these points on the 3D knee model were created, and the lengths of various fibers were digitally measured. Results: The average length changes were 9.1 ± 2.5 mm in F20, 9.1 ± 2.5 mm in F30, 8.1 ± 2.6 mm in F40, 6.9 ± 2.4 mm in F50, and 6.9 ± 1.7 mm in F60. There were significant differences in length changes of these 5 fibers (P < .001). The lengths of 2 superior fibers (F20 and F30) increased as the knee flexed from 0° to 30° and decreased as the knee flexed over 30°. The lengths of a middle fiber (F40) and an inferior fiber (F50) increased from 0° to 30°, reached a plateau from 30° to 60°, and then decreased from 60° to 120°. F60 showed an increase from 0° to 30°, and then a plateau pattern from 30° to 90°, followed by a decrease during further flexion. Conclusion: Superior fibers exhibited their maximum lengths at low flexion angles, and inferior fibers exhibited their maximum lengths at midflexion angles. The MPFL is a complex of functionally various fibers with some taut and others slack over the whole range of knee motion. Clinical Relevance: The results for lengths and length change patterns of various MPFL fibers are expected to serve as a theoretical background for anatomic double-bundle MPFL reconstruction.
The essential leadership and management skills of mid-level managers in non-profit organizations

The role of the middle manager in organizations is evolving. As organizations shift from strictly hierarchical structures to ones that are increasingly horizontal and interconnected through team-based collaborations, middle managers are being asked to assume more leadership responsibilities in addition to their traditional management duties. While there is agreement that both leadership and management skills are required for organizations to be successful, there is limited information on the specific skills that are required to both manage and lead from the middle. Mid-level managers who successfully develop both skill sets are well positioned for future leadership positions. Preparing middle managers for senior level responsibility is of particular importance to non-profit organizations which are currently facing a significant deficit in the leadership pipeline. To fully develop their human capital, senior level executives in non-profit organizations need to have a good understanding of the management and leadership skills they desire in their middle managers. The purpose of this study was to explore, with senior level executives in nonprofit organizations, the management and leadership skills they value in their middle managers. The study was designed using the Delphi Method approach of identification, shared evaluation and re-evaluation, and finally consensus among the executives, to determine the most desired and essential management and leadership skills. At the conclusion of the process, 11 senior level executives identified 11 management and leadership skills they believe are essential for effective mid-level management. 4 management skills were considered to be critical: (a) focused on the mission,
Superconductivity in Pt- and La-Doped BaFe2As2 Compounds Prepared by Solid-State Reaction

We report magnetization, resistivity, and heat capacity measurements on samples of BaFe<sub>2</sub>As<sub>2</sub>, BaFe<sub>1.9</sub>Pt<sub>0.1</sub>As<sub>2</sub>, and Ba<sub>0.7</sub>La<sub>0.3</sub>Fe<sub>1.9</sub>Pt<sub>0.1</sub>As<sub>2</sub> that have been prepared by solid-state reaction. Standard four-probe transport measurements in the temperature range 4.2-300 K showed that the substitution of non-isoelectronic Pt for Fe produced an electron-doped situation resulting in a superconductive phase transition at T<sub>c</sub> = 24 K. Furthermore, we observe that the coupled spin-density-wave/antiferromagnetic transition which occurs for the BaFe<sub>2</sub>As<sub>2</sub> sample at 140 K, as expected, also occurs in the Pt-doped BaFe<sub>1.9</sub>Pt<sub>0.1</sub>As<sub>2</sub> sample with only a small decrease in critical temperature to 138 K. We have also investigated in detail the superconducting state with magnetization measurements in the temperature range 5-400 K, up to a field of 9 T. From the magnetization data for BaFe<sub>1.9</sub>Pt<sub>0.1</sub>As<sub>2</sub>, we observe that T<sub>c</sub> = 21.7 K, which is in good agreement with the resistivity measurement. The zero-field cooled results correspond to a large Meissner fraction. In Ba<sub>0.7</sub>La<sub>0.3</sub>Fe<sub>1.9</sub>Pt<sub>0.1</sub>As<sub>2</sub>, we also see a large diamagnetic response, with a reduction in T<sub>c</sub> to 19.6 K. In addition, we analyzed heat capacity measurements for the electronic and phonon behavior of these materials. The analysis shows an excess entropy associated with the change in electronic behavior that is consistent with what is expected for Fe local moments, pointing to an electronic density of states that is based on a spin-fluctuation mechanism. We discuss the results in relation to a varying electronic density of states present in the samples and a possible pseudogap induced by addition of Pt.
Position sense at the human forearm in the horizontal plane during loading and vibration of elbow muscles

When blindfolded subjects match the position of their forearms in the vertical plane they rely on signals coming from the periphery as well as from the central motor command. The command signal provides a positional cue from the accompanying effort sensation required to hold the arm against gravity. Here we have asked, does a centrally generated effort signal contribute to position sense in the horizontal plane, where gravity cannot play a role? Blindfolded subjects were required to match forearm position for the unloaded arm and when flexors or extensors were bearing 10%, 25% or 40% of maximum loads. Before each match the reference arm was conditioned by contracting elbow muscles while the arm was held flexed or extended. For the unloaded arm conditioning led to a consistent pattern of errors which was attributed to signals from flexor and extensor muscle spindles. When elbow muscles were loaded the errors from conditioning converged, presumably because the spindles had become coactivated through the fusimotor system during the load‐bearing contraction. However, this convergence was seen only when subjects supported a static load. When they moved the load differences in errors from conditioning persisted. Muscle vibration during load bearing or moving a load did not alter the distribution of errors. It is concluded that for position sense of an unloaded arm in the horizontal plane the brain relies on signals from muscle spindles. When the arm is loaded, an additional signal of central origin contributes, but only if the load is moved.
RGB-D SLAM in Dynamic Environments Using Static Point Weighting

We propose a real-time depth edge based RGB-D SLAM system for dynamic environment. Our visual odometry method is based on frame-to-keyframe registration, where only depth edge points are used. To reduce the influence of dynamic objects, we propose a static weighting method for edge points in the keyframe. Static weight indicates the likelihood of one point being part of the static environment. This static weight is added into the intensity assisted iterative closest point (IAICP) method to perform the registration task. Furthermore, our method is integrated into a SLAM (Simultaneous Localization and Mapping) system, where an efficient loop closure detection strategy is used. Both our visual odometry method and SLAM system are evaluated with challenging dynamic sequences from the TUM RGB-D dataset. Compared to state-of-the-art methods for dynamic environment, our method reduces the tracking error significantly.
Petroleum potential of Oligocene lacustrine mudstones and coals at Dong Ho , Vietnam Ð an outcrop analogue to terrestrial source rocks in the greater Song Hong Basin

The outcrop of Oligocene age at Dong Ho, northern Vietnam, may constitute an immature analogue to offshore terrestrial source rocks in the greater Song Hong Basin. The outcrop includes an interval with two source rocks: (1) highly oil-prone carbonaceous mudstones containing kerogen types IIA and IIA/I, and with TOC contents from 6.48 to 16.89 wt%, and HI values from 472 to 690; and (2) oilprone humic coals (kerogen type III) with HI values from 200 to 242. The mudstones were deposited in oxygen-de®cient lakes, which on occasion were subject to marine in ̄uence, and the coals accumulated in freshwater peat-forming mires. The coals have broad activation energy (Ea) distributions, while the mudstones have Ea distributions characterised by a pronounced principal Ea. During arti®cial maturation about 16±17% of the organic carbon in the coals and 45±50% of the organic carbon in the mudstones participated in petroleum formation. The two source rocks primary generate oil and secondary generate gas, however, the mudstones realised the majority of their potential over a more narrow temperature range than the coals. The excellent generative potential of the terrestrial source rocks at Dong Ho is encouraging for offshore exploration for reservoirs charged by Cenozoic rift-lake successions. q 2001 Elsevier Science Ltd. All rights reserved.