Miracle-dz/UniFAR-FTUs huggingface dataset:
An epidemiological study of motor neuron disease in Hong Kong

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between I January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14. 12 (28- 89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 200 1) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.
A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations1

Background. The pharmacokinetics and immunodynamics of basiliximab were assessed in 39 pediatric de novo kidney allograft recipients to rationally chose a dose regimen for this age group. Methods. In study part 1, patients were given 12 mg/m2 of basiliximab by bolus intravenous injection before surgery and on day 4. An interim pharmacokinetic evaluation supported a fixed-dose approach for study part 2 in which infants and children received two 10-mg doses and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for analysis of basiliximab and soluble interleukin-2 receptor concentrations, flow cytometry, and screening for anti-idiotype antibodies. Results. Basiliximab clearance in infants and children (n=25) was reduced by approximately half compared with adults from a previous study and was independent of age (1–11 years), weight (9–37 kg), and body surface area (0.44–1.20 m2). Clearance in adolescents (12–16 years, n=14) approached or reached adult values. CD25-saturating basiliximab concentrations were maintained for 31±12 days in study part 1 with mg/m2 dosing and for 36±14 days in study part 2 based on the fixed-dose regimen (P =0.31). A single patient experienced a rejection episode during CD25 saturation. The duration of CD25 saturation in patients who experienced a rejection episode after desaturation did not differ from those who remained rejection-free for the full 6-month period: 34±6 days (n=6) vs. 35±14 days (n=33 patients);P =0.74. Anti-idiotype antibodies were detected in two patients; however, this did not influence the clearance of basiliximab or the duration of CD25 saturation. Conclusions. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients <35 kg should receive two 10-mg doses and those ≥35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose is given before surgery and the second on day 4 after transplantation.
Bilateral sphenoid wing metastases of prostate cancer presenting with extensive brain edema

A 76‐year‐old man insidiously developed diffuse neurological symptoms: cognitive decline, dysphagia, dysphasia and mental disturbance. Computed tomography of the cranium revealed widespread bilateral brain edema and symmetrical bilateral sphenoid wing hyperostosis. Adjacent to the hyperostosis that resembled skull base meningeomas, two separate parenchymatous temporal lobe lesions enhancing with contrast medium were observed. The patient had earlier been diagnosed to have prostatic carcinoma. Dexamethason therapy resulted in discontinuation of the neurological symptoms. The diagnosis of metastased adenocarcinoma of the prostate was confirmed histologically on autopsy after a sudden death from pneumonia. Intracranial metastases of prostate cancer may have a predilection site at the sphenoid wing, and can mimic a skull base meningeoma. Intracranial spread of prostatic adenocarcinoma should be considered in elderly men as a treatable cause of gradual neurological deterioration, especially if cranial malignancy or hyperostosis is found.
The CD25-binding antibody Daclizumab High-Yield Process has a distinct glycosylation pattern and reduced antibody-dependent cell-mediated cytotoxicity in comparison to Zenapax®

ABSTRACT The CD25-binding antibody daclizumab high-yield process (DAC HYP) is an interleukin (IL)-2 signal modulating antibody that shares primary amino acid sequence and CD25 binding affinity with Zenapax®, a distinct form of daclizumab, which was approved for the prevention of acute organ rejection in patients receiving renal transplants as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. Comparison of the physicochemical properties of the two antibody forms revealed the glycosylation profile of DAC HYP differs from Zenapax in both glycan distribution and the types of oligosaccharides, most notably high-mannose, galactosylated and galactose-α-1,3-galactose (α-Gal) oligosaccharides, resulting in a DAC HYP antibody material that is structurally distinct from Zenapax. Although neither antibody elicited complement-dependent cytotoxicity in vitro, DAC HYP antibody had significantly reduced levels of antibody-dependent cell-mediated cytotoxicity (ADCC). The ADCC activity required natural killer (NK) cells, but not monocytes, suggesting the effects were mediated through binding to Fc-gamma RIII (CD16). Incubation of each antibody with peripheral blood mononuclear cells also caused the down-modulation of CD16 expression on NK cells and the CD16 down-modulation was greater for Zenapax in comparison to that observed for DAC HYP. The substantive glycosylation differences between the two antibody forms and corresponding greater Fc-mediated effector activities by Zenapax, including cell killing activity, manifest as a difference in the biological function and pharmacology between DAC HYP and Zenapax.
Low-density lipoprotein cholesterol and suicidal behaviour in a large sample of first-episode psychosis patients

Abstract Objectives: Our aims were to confirm the relationship between lipid and lipoprotein concentrations and suicidal behaviour in first-episode psychosis (FEP) patients. Methods: Suicidal behaviour was explored in a large FEP sample (N = 383). Baseline lipid profile was compared between those who attempted or completed suicide and those who not presented suicidal behaviour. Results: Low-density lipoprotein cholesterol (LDL-c) (OR = 0.99, 95% CI= 0.98–1.00) and depressive symptoms (OR = 1.15, 95% CI = 1.06–1.24) were significantly related with suicidal behaviour. Conclusions: Lipid profile test may be considered in the assessment of suicide risk in psychosis and LDL-c an important biological marker.
Assessment of disorder predictions in CASP7

Intrinsically unstructured regions in proteins have been associated with numerous important biological cellular functions. As measuring native disorder experimentally is technically challenging, computational methods for prediction of disordered regions in a protein have gained much interest in recent years. As part of the seventh Critical Assessment of Techniques for Protein Structure Prediction (CASP7), we have assessed 19 methods for disorder prediction based on their results for 96 target proteins. Prediction accuracy was assessed using detailed numerical comparison between the predicted disorder and the experimental structures. On average, methods participating in CASP7 have improved accuracy in comparison to the previous assessment in CASP6. Overall, however, no improvement over the best methods in CASP6 was observed in CASP7. Significant differences between different prediction methods were identified with regard to their sensitivity and specificity in correctly predicting ordered and disordered residues based on a protein target sequence, which is of relevance for practical applications of these computational tools. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Investigation of cure kinetics and its effect on adhesion strength of nonconductive adhesives used in flip chip assembly

The reaction kinetics of a commercial fast cure nonconductive adhesive has been systematically investigated using differential scanning calorimetry. Samples were isothermally cured at temperatures from 120 to 160/spl deg/C and dynamically cured at ramp rates between 5 and 20/spl deg/C/min. A good agreement between the autocatalytic kinetic model prediction and experimental results was demonstrated. Deviation occurred at high degrees of cure for curing below 140/spl deg/C due to the occurrence of vitrification. Additionally, by comparing the dynamic cure prediction with the isothermal experiment, good agreements and equivalence were demonstrated. As such, it is possible to predict the isothermal reaction behavior of fast cure materials at high temperature provided that the variation between the actual temperature of the heating system and the setting temperature is not large. Furthermore, the effect of curing process on the adhesion strength has been demonstrated by testing the shear strength of lap joint specimens. It was found that the evolution of adhesion strength was largely dependent on the buildup of mechanical properties during the curing process. At low and medium degrees of cure, cohesive and adhesive failures were respectively observed, while at high degrees of cure, adhesion strength surpassing the shear strength of the solder mask was observed. The sharp increase in adhesion strength was observed to coincide with the gelation point marked by the crossover between the storage and loss modulii, thus suggesting that the contributors to adhesion strength include mechanical interlocking as well as chemical bonding, as evidenced by buildup of storage modulus and mechanical strength of the adhesive.
Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery

Background The efficacy of mesenchymal stem cell (MSC) transplantation in ischemic stroke might depend on the timing of administration. We investigated the optimal time point of MSC transplantation. After MSC treatment, we also investigated the expression of matrix metalloproteinases (MMPs), which play a role in vascular and tissue remodeling. Methods Human bone marrow-derived MSCs (2 × 106, passage 5) were administrated intravenously after permanent middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats. First, we determined the time point of MSC transplantation that led to maximal neurological recovery at 1 h, 1 day, and 3 days after MCAO. Next, we measured activity of MMP-2 and MMP-9, neurological recovery, infarction volume, and vascular density after transplanting MSCs at the time that led to maximal neurological recovery. Results Among the MSC-transplanted rats, those of the MSC 1-hour group showed maximal recovery in the rotarod test (P = 0.023) and the Longa score (P = 0.018). MMP-2 activity at 1 day after MCAO in the MSC 1-hour group was significantly higher than that in the control group (P = 0.002), but MMP-9 activity was not distinct. The MSC 1-hour group also showed smaller infarction volume and higher vascular density than did the control group. Conclusions In a permanent model of rodent MCAO, very early transplantation of human MSCs (1 h after MCAO) produced greater neurological recovery and decreased infraction volume. The elevation of MMP-2 activity and the increase in vascular density after MSC treatment suggest that MSCs might help promote angiogenesis and lead to neurological improvement during the recovery phase after ischemic stroke.
Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry

Objective: To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β). Methods: A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method. A marginal Cox model was used to analyse time to first relapse, 3-month confirmed disability progression and treatment discontinuation in the matched sample. A signed-rank test was used to compare Expanded Disability Status Scale (EDSS) change from baseline. Results: Rituximab was associated with a reduction in ARR (0.003; 95% confidence interval (CI) = 0.001, 0.009) relative to IFN-β/GA (0.026; 95% CI = 0.020, 0.033) (p < 0.001). Rituximab was associated with an 87% reduction in the relapse rate (hazard ratio (HR) = 0.13; 95% CI = 0.04, 0.41) and an 85% reduction in the discontinuation rate (HR = 0.15; 95% CI = 0.11, 0.20) relative to IFN-β/GA. EDSS regression from baseline was greater in the rituximab group at 12 and 24 months. Conclusion: Rituximab appears to be superior to first-generation disease-modifying treatments (DMTs) with respect to relapse control and tolerability, whereas superiority on disability outcomes is less clear.
Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes.

Intravenous heparin, a fundamental therapy in the treatment of patients with acute coronary syndromes, acts by inhibiting thrombin and activated factors X, IX, XI, and XII. It has also been demonstrated that heparin reduces plasma fibrinopeptide A, a marker of thrombin activity, but it is unknown whether it decreases prothrombin fragment 1+2, an indirect marker of thrombin generation. We measured the plasma levels of prothrombin fragment 1+2, fibrinopeptide A, and antithrombin III in 64 consecutive patients with unstable angina or myocardial infarction receiving intravenous heparin. Blood samples were obtained at baseline (before any treatment) and then at 90 minutes and 24 and 48 hours after the administration of an intravenous bolus of heparin (5000 IU) followed by a continuous infusion of 1000 IU per hour to maintain activated partial thromboplastin time at more than double its baseline levels. In comparison with baseline, there was a significant decrease in fibrinopeptide A at 90 minutes and at 24 and 48 hours (baseline, 2.3 nmol/L; 90 minutes, 1.15 nmol/L; 24 hours, 1.4 nmol/L; 48 hours, 1.2 nmol/L; P < .0001) but no change in prothrombin fragment 1+2 levels (baseline, 1.27 nmol/L; 90 minutes, 1.3 nmol/L; 24 hours, 1.33 nmol/L; 48 hours, 1.29 nmol/L; P = NS). Antithrombin III activity decreased at 24 and 48 hours (baseline, 108%; 24 hours, 97%; 48 hours, 95%; P < .0001). Hence, in patients with acute coronary syndromes, intravenous heparin at a dose reaching an activated partial thromboplastin time that adequately suppresses thrombin activity does not suppress increased thrombin generation.
Magnetic Resonance Tissue Phase Mapping of Myocardial Motion: New Insight in Age and Gender

Background—An exact understanding of normal age- and gender-matched regional myocardial performance is an essential perquisite for the diagnosis of heart disease. Magnetic resonance phase-contrast imaging (tissue phase mapping) enabling the analysis of segmental, 3-directional myocardial velocities with high temporal resolution (13.8 ms) was used to assess left ventricular motion. Methods and Results—Radial, long-axis, and rotational myocardial velocities were acquired in 58 healthy volunteers (3 age groups, 29 women) in left ventricular basal, midventricular, and apical short-axis locations. For increased age, reduced (P<0.003) and prolonged long-axis and radial velocities (P<0.05) during diastole and reduced long-axis velocities (P<0.001) and apical rotation (P<0.005) during systole were found for both genders. Women demonstrated a reduced systolic twist (P=0.009), apical rotation (P=0.01), and systolic radial velocities (P<0.02) compared with men. Segmental analysis of long-axis motion with aging revealed differences in regional reduction of systolic (lateral 52% versus 30%) and diastolic (lateral 57% versus 41%) velocities in women compared with men. In basal segments, young women demonstrated higher long-axis velocities (+11% during diastole) than men, whereas this difference was reversed in older subjects (same segments, −20%). In addition, increased age resulted in a prolonged time to peak diastolic apical rotation (P<0.04) in women compared with men. Conclusions—Age and gender strongly influence regional myocardial motion. Tissue phase mapping provides a comprehensive quantitative analysis of all myocardial velocities with high temporal and spatial resolution. The knowledge of the detected age- and gender-related differences in myocardial motion is fundamental for further investigations of cardiac disease. Clinical Trial Registration—http://www.zks. uni-freiburg.de/uklreg/php/suchergebnis_all. php. Identifier: UKF001739
On the asymptotic performance of TBMA with multichannel diversity over fading channels

In distributed detection for wireless sensor networks, multiple access schemes and channel conditions affect the performance of data fusion at a fusion center together with communication constraints (bandwidth and transmission energy). For an efficient channel use, the type-based multiple access (TBMA) has been proposed by Mergen et al. Since the performance of TBMA is not satisfactory for zero-mean fading channels, it could be extended to exploit multichannel diversity for better performance, which is called TBMA with multichannel diversity (TBMA-MD) in this paper. We study the performance of TBMA-MD over Rayleigh fading channels and show that the error probability decays exponentially in the multichannel diversity gain (not in the number of sensors). Error exponents are also derived for binary hypotheses with closed-form expressions for some cases.
Serum profiles of vitamins A, E and D in mares and foals during different seasons.

Twenty mares and 15 foals of the Finnhorse breed were used to determine serum levels of vitamins A, E and D during different seasons. Monthly serum samples were analyzed from mares for 22 mo and from foals for 13 mo after birth. The horses were kept on pasture from early June until early October and in stables during the winter months. Seasonal differences (P less than .001) were found in serum retinol, retinol to protein ratio, alpha-tocopherol and alpha-tocopherol to cholesterol ratio. Values were lowest from February through May and highest from June through August. Serum levels of retinol and alpha-tocopherol of the foals were much lower (P less than .001) than in mares during the first 4 mo of life. As in the mares, serum levels of retinol and alpha-tocopherol decreased (P less than .001) in winter. At 1 yr of age, serum levels of these vitamins increased rapidly on pasture to values that were close to those found in adult horses. Serum 25-hydroxyvitamin D levels were very low throughout the year. However, a small seasonal variation also was found in 25-hydroxyvitamin D concentrations in the mares. Serum 1,25-dihydroxyvitamin D levels in pregnant mares in winter were similar to those found in lactating mares in summer. These levels also were low compared with those in animals of other species. (ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation and optimisation of a targetcontrolled infusion system for administering propofol to dogs as part of a total intravenous anaesthetic technique during dental surgery

The performance of a modified target-controlled infusion system was investigated in 16 dogs undergoing routine dental work, by comparing the predicted concentrations of propofol in venous blood samples with direct measurements; the optimum targets for the induction and maintenance of anaesthesia were also identified. The performance of a target-controlled infusion system is considered clinically acceptable when the median prediction error, a measure of bias, is not greater than ±10 to 20 per cent, and the median absolute performance error, a measure of the accuracy, is not greater than 20 to 30 per cent. The results fell within these limits indicating that the system performed adequately. The optimal induction target was 3 μg/ml, and anaesthesia of adequate depth and satisfactory quality was achieved with maintenance targets of between 2.5 and 4.7 μg/ml propofol. The system was easy to use and the quality of anaesthesia was adequate for dental work.
Genetic variation associated with bortezomib-induced peripheral neuropathy

Objective To develop a predictive genetic signature for the development of bortezomib-induced peripheral neuropathy (PN). Methods Two thousand and sixteen single-nucleotide polymorphisms (SNPs) were genotyped in 139 samples from myeloma patients treated with bortezomib–melphalan–prednisone in the VISTA phase 3 trial. Single-marker association analysis for PN onset and time/cumulative dose to PN onset using the Cox proportional hazards model and multiple covariates was performed under additive, dominant, and recessive genotypic models, followed by correction for multiplicity. Associations were also pursued in a cohort of 212 samples from patients treated with bortezomib–dexamethasone in the IFM 2005-01 phase 3 trial. Results In the VISTA cohort, after Bonferroni correction, two SNPs significantly associated with time to onset of PN [CTLA4 rs4553808, false discovery rate (FDR)=0.002] and time to onset of grade of at least 2 PN (PSMB1 rs1474642, FDR=0.014). Using FDR less than 0.05 as the threshold, two additional SNPs significantly associated with time to onset of grade of at least 2 (CTSS rs12568757, FDR=0.027) or grade of at least 3 PN (GJE1 rs11974610, FDR=0.041). DYNC1I1 rs916758 significantly associated (FDR=0.012) with cumulative dose to onset of grade of at least 2 PN. These associations were generally not detected in the IFM 2005-01 cohort, although CTLA4 rs4553808 showed the same trend in association with time to onset (P=0.138). In addition, in the IFM 2005-01 cohort, TCF4 rs1261134 significantly associated with onset of any neurologic event (FDR=0.048). Conclusion Genes associated with immune function (CTLA4, CTSS), reflexive coupling within Schwann cells (GJE1), drug binding (PSMB1), and neuron function (TCF4, DYNC1I1) associated with bortezomib-induced PN in this study.