Miracle-dz/UniFAR-FTUs huggingface dataset:
A Review of A Priori Regression Models for Warfarin Maintenance Dose Prediction

A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.
Stochastic fluctuations in metabolic pathways

Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of downstream targets in a network. Here, we develop an analytic framework to investigate the phenomenon of noise correlation in molecular networks. Specifically, we focus on the metabolic network, which is highly interlinked, and noise properties may constrain its structure and function. Motivated by the analogy between the dynamics of a linear metabolic pathway and that of the exactly soluble linear queuing network or, alternatively, a mass transfer system, we derive a plethora of results concerning fluctuations in the abundance of intermediate metabolites in various common motifs of the metabolic network. For all but one case examined, we find the steady-state fluctuation in different nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations in enzyme levels only affect local properties and do not propagate elsewhere into metabolic networks, and intermediate metabolites can be freely shared by different reactions. Our approach may be applicable to study metabolic networks with more complex topologies or protein signaling networks that are governed by similar biochemical reactions. Possible implications for bioinformatic analysis of metabolomic data are discussed.
Preischemic Hyperglycemia Leads to Delayed Postischemic Hyperthermia

Temperature alterations are known to influence the outcome of transient ischemia, even when instituted in the postischemic period. Since preischemic hyperglycemia aggravates ischemic brain damage, the question of whether hyperglycemic animals become hyperthermic arose. To explore this possibility, we measured body temperature telemetrically in normoglycemic and hyperglycemic rats subjected to 10 minutes of forebrain ischemia at a body (and brain) temperature of 37°C. Methods Isoflurane-anesthetized animals were subjected to 10 minutes of forebrain ischemia under normoglycemic or hyperglycemic conditions. Temperature changes after ischemia were measured by means of a telemetric temperature coil. Results In normoglycemic animals, temperature decreased to 35.6±1.1°C (mean±SD) during the first 4 hours of recovery, after which it gradually increased to normal values (38°C). Hyperglycemic animals behaved differently in that they remained normothermic for approximately 10 hours during recovery and later became hyperthermic, with core temperatures rising above 39°C. The rise in temperature was not due to the osmotic load of the glucose administered because infusion of mannitol, which gave a comparable increase in plasma osmolality, failed to cause delayed postischemic hyperthermia. Excessive hypercapnia during ischemia in normoglycemic animals, which produces cerebral acidosis of a magnitude similar to that of hyperglycemia and is known to aggravate ischemic lesions, likewise failed to induce hyperthermia. When postischemic seizures ensued in hyperglycemic subjects, temperature was 39.8±0.6°C. Animals with seizures invariably died. To evaluate the influence of postischemic hyperthermia on the outcome, an additional series of experiments was performed in which delayed hyperthermia was avoided by gentle cooling (n=6) or by acetaminophen administration (n=5). Although these procedures prevented delayed hyperthermia, they neither blocked seizure induction nor affected the fatal outcome. Postischemic seizures developed when the core temperatures of animals were 37.9±0.1°C and 37.8±0.2°C in the cooled and acetaminophen-treated groups, respectively. Conclusions The results suggest that both delayed hyperthermia and delayed seizures in hyperglycemic animals are caused by the aggravated damage incurred by these animals during or immediately after the ischemic insult.
English Benchmark Policy for Graduation in Taiwan’s Higher Education: Investigation and Reflection

Encouraged by the Ministry of Education (MOE), an increasing number of universities and colleges in Taiwan have started to set their own English benchmarks for graduation using external standardized language tests as exit exams. The present study investigated and reflected on the implementation of this policy at two technological universities in Taiwan by answering two research questions: (1) How did college administrators, teachers and students perceive the policy? (2) What washback effects did the English graduation benchmark policy bring about? A mixed-methods approach was adopted for the study. The results show that although there was a social consensus about the implementation of the policy, the policy did not seem to have achieved what the MOE had expected due to its limited and weak washback on teaching and learning. It is suggested that the English graduation requirements might have to be modified in the subsequent policies for more meaningful and practical results.
The Effect of β-Glycerophosphate Crosslinking on Chitosan Cytotoxicity and Properties of Hydrogels for Vaginal Application

Mucoadhesive gelling systems based on chitosan and chitosan/β-glycerophosphate (β-GP) were developed in order to increase clotrimazole residence time in the vaginal cavity. Ex vivo mucoadhesiveness using porcine vaginal mucosa followed with mechanical, viscoelastic, and swelling properties of prepared hydrogels were evaluated. Drug-free, sterile, unmodified, and β-GP crosslinked chitosan were investigated for the in vitro cytotoxicity in CRL 2616 human vaginal mucosa cells using MTT assay, fluorescent microscopy, and flow cytometry analysis. Chitosan/β-GP hydrogels exhibited pseudoplastic and thixotropic properties. Ionic interaction between β-GP and chitosan improved mechanical properties of hydrogels in terms of hardness, cohesiveness, and compressibility. The hydrogels’ ability to interact with porcine vaginal mucosa (measured as force of detachment and work of adhesion) was comparable to those obtained with reference mucoadhesive gel Replens™. Surprisingly, greater mucoadhesive properties were noticed for chitosan/β-GP hydrogels. The cytotoxic effect of unmodified and β-GP crosslinked chitosan was hardly affected by chitosan molecular weight, exhibited mainly through inducing apoptosis, and was found to be significantly lower in the presence of chitosan/β-GP. Furthermore, the higher amount of β-GP was used to crosslink chitosan, the lower cytotoxic effect was observed.
Descriptive epidemiology of colorectal cancer in University Malaya Medical Centre, 2001 to 2010.

BACKGROUND Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes. MATERIALS AND METHODS Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05. RESULTS The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%). CONCLUSIONS Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age.
Large-Scale Allelotype of Pancreaticobiliary Carcinoma Provides Quantitative Estimates of Genome-Wide Allelic Loss

Studies of the allelotype of human cancers have provided valuable insights into those chromosomes targeted for genetic inactivation during tumorigenesis. We present the comprehensive allelotype of 82 xenografted pancreatic or biliary cancers using 386 microsatellite markers and spanning the entire genome at an average coverage of 10 cM. Allelic losses were nonrandomly distributed across the genome and most prevalent for chromosome arms 9p, 17p, and 18q (>60%), sites of the known tumor suppressor genes CDKN2A, TP53, and MADH4. Moderate rates of loss (at any one locus) were noted for chromosome arms 3p, 6q, 8p, 17q, 18p, 21q, and 22q (40–60%). A mapping of individual loci of allelic loss revealed 11 “hot spots” of loss of heterozygosity (>30%) in addition to loci near known tumor suppressor genes, corresponding to 3p, 4q, 5q, 6q, 8p, 12q, 14q, 21q, 22q, and the X chromosome. The average genomic fractional allelic loss was 15.3% of all tested markers for the 82 xenografted cancers, with allelic loss affecting as little as 1.5% to as much as 32.1% of tested loci, a remarkable 20-fold range. We determined the chromosome location (in cM) of each of the 386 markers used based on mapping data available from the National Center for Biotechnology Information, and we provide the first distance-based estimates of chromosome material lost in a human epithelial cancer. Specifically, we found that the cumulative size of allelic losses ranged from 58 to 1160 cM, with an average loss of 561.32 cM/tumor. We compared the genomic fractional allelic loss of each xenografted cancer with known clinicopathological features for each patient and found a significant correlation with smoking status (P < 0.01). These findings offer new loci for investigation of the genetic alterations common to pancreaticobiliary cancers and aid the understanding of mechanisms of allelic loss in human carcinogenesis.
CONVERGENCE OF LINEAR AND NON-LINEAR VERSIONS OF VICSEK’S MODEL

The Vicsek model describes the evolution of a system composed by different agents moving in the plane. Each agent has a constant speed and updates its heading using a local rule depending on the headings of its “neighbors”. Although the original model by Vicsek is non-linear, most of the convergence results obtained so far deal with linearized versions. In this paper, we introduce a new linear model in which the relative importance of each neighbor can vary with the distance and we prove the convergence of all the agents headings. For this purpose, we derive a theorem on the convergence of long products of stochastic products that applies to infinite set of matrices. Using this result we also prove convergence properties for the original non-linear Vicsek model. Moreau [7] obtains similar results to ours but using a proof technique based on convexity and system theory. We present here proofs that are based on elementary linear algebra tools. The results we obtain are somewhat weaker than those of Moreau but have the advantage of being indistinctly applicable to continuous and discontinuous systems.
Electroencephalographic, volumetric, and neuropsychological indicators of seizure focus lateralization in temporal lobe epilepsy.

CONTEXT Anterior temporal lobectomy is an effective treatment for medically intractable temporal lobe seizures. Identification of seizure focus is essential to surgical success. OBJECTIVE To examine the usefulness of presurgical electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological data in the lateralization of seizure focus. DESIGN Presurgical EEG, MRI, and neuropsychological data were entered, independently and in combination, as indicators of seizure focus lateralization in discriminant function analyses, yielding correct seizure lateralization rates for each set of indicators. SETTING Comprehensive Epilepsy Program, Shands Teaching Hospital, University of Florida, Gainesville. PATIENTS Forty-four right-handed adult patients who ultimately underwent successful anterior temporal lobectomy. Left-handed patients, those with less-than-optimal surgical outcome, and any patients with a history of neurological insult unrelated to seizure disorder were excluded from this study. MAIN OUTCOME MEASURES For each patient presurgical EEG was represented as a seizure lateralization index reflecting the numbers of seizures originating in the left hemisphere, right hemisphere, and those unable to be lateralized. Magnetic resonance imaging data were represented as left-right difference in hippocampal volume. Neuropsychological data consisted of mean scores in each of 5 cognitive domains. RESULTS The EEG was a better indicator of lateralization (89% correct) than MRI (86%), although not significantly. The EEG and MRI were significantly superior to neuropsychological data (66%) (P=.02 and .04, respectively). Combining EEG and MRI yielded a significantly higher lateralization rate (93%) than EEG alone (P<.01). Adding neuropsychological data improved this slightly (95%). CONCLUSIONS The EEG and MRI were of high lateralization value, while neuropsychological data were of limited use in this regard. Combining EEG, MRI, and neuropsychological improved focus lateralization relative to using these data independently.
Clonazepam Treatment of Pathologic Aerophagia in Children with Mental Retardation

Purpose Pathologic aerophagia (PA) may lead to bowel perforation or volvulus in mentally retarded patients. The authors investigated the effects of clonazepam on the management of PA in children with severe to profound mental retardation (MR). Methods This study was undertaken as a retrospective case analysis of 21 PA patients with MR who were followed for over 12 months and diagnosed as having PA. Patients were assigned to two management groups, that is, to a clonazepam randomized open-labeled, treatment group or a reassurance group. The following were recorded and analyzed; age, response, remission rate to clonazepam treatment, and the side effect of clonazepam. It was defined positive response (response+) as being symptom-free for a whole week within 1 month of commencing treatment and remission(+) as being symptom-free for a whole month within 6 months of treatment. Results The average age of the 21 PA children with MR was 10 years and 13 patients were female. Symptom duration before diagnosis of PA was 7 months. Clinical features of the clonazepam-trial group (n=11) and the reassurance group (n=10) were non-significantly different. Response(+) was achieved by 2 patients (18.2%) in the clonazepam-trial group and by no patient in the reassurance group. Remission(+) was achieved by 6 patients (54.5%) in the clonazepam-trial group and by one patient (10%) in the reassurance group (p=0.040). Conclusion When PA children with MR with severe bowel distention are considered for surgical treatment to prevent acute abdomen, a trial of clonazepam could be recommended.
Spectroscopic Survey of the Galaxy with Gaia II. The expected science yield from the Radial Velocity Spectrometer

The Gaia mission is designed as a Galaxy explorer, and will measure simultaneously, in a survey mode, the five or six phase-space parameters of all stars brighter than 20th magnitude, as well as providing a description of their astrophysical characteristics. These measurements are obtained by combining an astrometric instrument with micro-arcsecond capabilities, a photometric system giving the magnitudes and colours in 15 bands and a medium-resolution spectrograph named the Radial Velocity Spectrometer (RVS). The latter instrument will produce spectra in the 848- to 874-nm wavelength range, with a resolving power R = 11500, from which radial velocities, rotational velocities, atmospheric parameters and abundances can be derived. A companion paper has presented the characteristics of the RVS and its performance. The present paper details the outstanding scientific impact of this important part of the Gaia satellite on some key open questions in present-day astrophysics. The unbiased and simultaneous acquisition of multi-epoch radial velocities and individual abundances of key elements in parallel with the astrometric parameters is essential for the determination of the dynamical state and formation history of our Galaxy. Moreover, for stars brighter than V similar or equal to 15, the resolving power of the RVS will give information about most of the effects that influence the position of a star in the Hertzsprung-Russell diagram, placing unprecedented constraints on the age, internal structure and evolution of stars of all types. Finally, the RVS multi-epoch observations are ideally suited to the identification, classification and characterization of the many types of double, multiple and variable stars.
Increases of cardiac troponin in conditions other than acute coronary syndrome and heart failure.

BACKGROUND Although cardiac troponin (cTn) is a cornerstone marker in the assessment and management of patients with acute coronary syndrome (ACS) and heart failure (HF), cTn is not diagnostically specific for any single myocardial disease process. This narrative review discusses increases in cTn that result from acute and chronic diseases, iatrogenic causes, and myocardial injury other than ACS and HF. CONTENT Increased cTn concentrations have been reported in cardiac, vascular, and respiratory disease and in association with infectious processes. In cases involving acute aortic dissection, cerebrovascular accident, treatment in an intensive care unit, and upper gastrointestinal bleeding, increased cTn predicts a longer time to diagnosis and treatment, increased length of hospital stay, and increased mortality. cTn increases are diagnostically and prognostically useful in patients with cardiac inflammatory diseases and in patients with respiratory disease; in respiratory disease cTn can help identify patients who would benefit from aggressive management. In chronic renal failure patients the diagnostic sensitivity of cTn for ACS is decreased, but cTn is prognostic for the development of cardiovascular disease. cTn also provides useful information when increases are attributable to various iatrogenic causes and blunt chest trauma. SUMMARY Information on the diagnostic and prognostic uses of cTn in conditions other than ACS and heart failure is accumulating. Although increased cTn in settings other than ACS or heart failure is frequently considered a clinical confounder, the astute physician must be able to interpret cTn as a dynamic marker of myocardial damage, using clinical acumen to determine the source and significance of any reported cTn increase.
The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores

A hydrophobic constriction site can act as an efficient barrier to ion and water permeation if its diameter is less than the diameter of an ion's first hydration shell. This hydrophobic gating mechanism is thought to operate in a number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA, MthK and KvAP). Simplified pore models allow one to investigate the primary characteristics of a conduction pathway, namely its geometry (shape, pore length, and radius), the chemical character of the pore wall surface, and its local flexibility and surface roughness. Our extended (about 0.1 µs) molecular dynamic simulations show that a short hydrophobic pore is closed to water for radii smaller than 0.45 nm. By increasing the polarity of the pore wall (and thus reducing its hydrophobicity) the transition radius can be decreased until for hydrophilic pores liquid water is stable down to a radius comparable to a water molecule's radius. Ions behave similarly but the transition from conducting to non-conducting pores is even steeper and occurs at a radius of 0.65 nm for hydrophobic pores. The presence of water vapour in a constriction zone indicates a barrier for ion permeation. A thermodynamic model can explain the behaviour of water in nanopores in terms of the surface tensions, which leads to a simple measure of ‘hydrophobicity’ in this context. Furthermore, increased local flexibility decreases the permeability of polar species. An increase in temperature has the same effect, and we hypothesize that both effects can be explained by a decrease in the effective solvent–surface attraction which in turn leads to an increase in the solvent–wall surface free energy.