Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of myasthenia gravis by immunoadsorption of plasma

Article abstract—We treated 16 patients with moderately severe to severe generalized myasthenia gravis (MG) by immunoadsorption (perfusion through a resin that adsorbs proteins) of 2,500 ml plasma on each of four alternate days. Fourteen patients who completed treatment all had significant improvement in strength (6 excellent, 6 good, and 2 fair), which began a mean of 42 hours after the first immunoadsorption, reached a maximum 4 days after the fourth immunoadsorption (mean, 250% of baseline strength), and returned to baseline over a mean of 2 months. Thirty-seven grams of plasma proteins were removed during each immunoadsorption, which required no replacement, compared with 175 grams during plasma exchange, which requires replacement with albumin. Serum or plasma concentration of all proteins fell, more so for most of the larger proteins than for the smaller ones: acetylcholine receptor antibody (AChR Ab) fell to a mean of 23% of original level, fibrinogen to 26%, C4 to 29%, IgM to 33%, IgG to 35%, CH50 to 41%, C3 to 42%, IgA to 54%, and albumin to 76%. All proteins, including AChR Ab, returned to their original levels within 1 to 3 weeks after the last immunoadsorption, while improvement in strength lasted a mean of 6 weeks longer. One seronegative patient had excellent improvement lasting more than a month. Activated complement C5a and white blood cell count rose during each immunoadsorption, while activated complement C3a fell, and each returned to its original level within hours. Eight patients had transient symptomatic hypotension attributable to withdrawal of blood more rapidly than it was returned; this hypotension was prevented or ameliorated by intravenous saline. Immunoadsorption is safe and effective in the management of MG and may be preferable to plasma exchange, because protein replacement is unnecessary and side effects may be less marked.
Rapid Detection of Vancomycin-Intermediate Staphylococcus aureus by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

ABSTRACT Vancomycin is the standard of care for the treatment of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Infections with vancomycin-nonsusceptible MRSA, including vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA), are clinically challenging and are associated with poor patient outcomes. The identification of VISA in the clinical laboratory depends on standard susceptibility testing, which takes at least 24 h to complete after isolate subculture, whereas hVISA is not routinely detected in clinical labs. We therefore sought to determine whether VISA and hVISA can be differentiated from vancomycin-susceptible S. aureus (VSSA) using the spectra produced by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Strains of MRSA were characterized for vancomycin susceptibility phenotype by broth microdilution and modified population analysis. We tested 21 VISA, 21 hVISA, and 38 VSSA isolates by MALDI-TOF MS. Susceptibility phenotypes were separated by using a support vector machine (SVM) machine learning algorithm. The resulting model was validated by leave-one-out cross validation. Models were developed and validated by using spectral profiles generated under various subculture conditions, as well as with and without hVISA strains. Using SVM, we correctly identified 100% of the VISA and 97% of the VSSA isolates with an overall classification accuracy of 98%. Addition of hVISA to the model resulted in 76% hVISA identification, 100% VISA identification, and 89% VSSA identification, for an overall classification accuracy of 89%. We conclude that VISA/hVISA and VSSA isolates are separable by MALDI-TOF MS with SVM analysis.
An energy-efficient on-chip memory structure for variability-aware near-threshold operation

On-chip memory is one of the most energy consuming components in processors. Aggressive voltage scaling to the sub-/near-threshold region is thus applied even to the memory used for ultra-low power applications. In this paper, an energy-efficient cell-based memory structure which is stably working with a near-threshold operating voltage is proposed. The circuit simulation using a commercial 28-nm technology shows that the energy consumption for the readout operation in our memory proposed here is up to 61% less than the energy dissipated in an existing cell-based memory and a conventional SRAM circuit. The simulation using a foundry provided Monte Carlo package also shows that the 3σ worst case read-access time of our cell-based memory is comparable to that of the SRAM circuit.
Different secondary structure elements as scaffolds for protein folding transition states of two homologous four‐helix bundles

Comparison of the folding processes for homologue proteins can provide valuable information about details in the interactions leading to the formation of the folding transition state. Here the folding kinetics of 18 variants of yACBP and 3 variants of bACBP have been studied by Φ‐value analysis. In combination with Φ‐values from previous work, detailed insight into the transition states for folding of both yACBP and bACBP has been obtained. Of the 16 sequence positions that have been studied in both yACBP and bACBP, 5 (V12, I/L27, Y73, V77, and L80) have high Φ‐values and appear to be important for the transition state formation in both homologues. Y31, A34, and A69 have high Φ‐values only in yACBP, while F5, A9, and I74 have high Φ‐values only in bACBP. Thus, additional interactions between helices A2 and A4 appear to be important for the transition state of yACBP, whereas additional interactions between helices A1 and A4 appear to be important for the transition state of bACBP. To examine whether these differences could be assigned to different packing of the residues in the native state, a solution structure of yACBP was determined by NMR. Small changes in the packing of the hydrophobic side‐chains, which strengthen the interactions between helices A2 and A4, are observed in yACBP relative to bACBP. It is suggested that different structure elements serve as scaffolds for the folding of the 2 ACBP homologues. Proteins 2005. © 2005 Wiley‐Liss, Inc.
A General Model of Abstention Under Compulsory Voting*

Invalid voting and absenteeism are alternative sources of abstention under compulsory voting. Previous research failed to systematically study the mechanisms behind each form of non-voting and the relationships between them. We develop an analytical framework and an empirical strategy to jointly examine invalid voting and absenteeism in Brazil, the world’s largest democracy with mandatory voting. Using Bayesian inferential methods and analyzing both individual and district-level data, we show that less educated and politically knowledgeable citizens are less likely to vote and, when they do, they are typically unable to successfully complete their ballot. Unlike absenteeism, invalid voting also has a political dimension reflecting voters’ disenchantment with elections and democratic performance. Both sources of abstention coexist and, together, undermine electoral participation.
Numerical chromosome abnormalities in 8-cell embryos generated from γ-irradiated male mice in the absence and presence of vitamin E

Purpose: To investigate the effects of γ-rays on male NMRI mice, in the absence or presence of vitamin E, on abnormalities in chromosome number in 8-cell embryos generated after mating with non-irradiated female mice. Materials and methods: The 8 – 11 week old male NMRI mice were irradiated whole body with 4 Gy of γ-rays alone or in combination with 200 international units (IU)/kg vitamin E administered 1 h prior to irradiation. After 4 days, they were mated at weekly intervals with superovulated, non-irradiated female mice in successive 6 weekly periods. About 68 h post coitous (p.c.), 8-cell embryos were fixed on slides using standard methods in order to screen for abnormalities in chromosome number. Results: In control embryos, 8% of metaphases were aneuploid whereas in embryos generated from irradiated mice, the frequency of aneuploidy increased dramatically at all post irradiation sampling times (p < 0.001). Administration of vitamin E one hour before irradiation, significantly decreased chromosomal aberrations in all 6 groups (p < 0.05). Conclusion: Data indicate that γ-irradiation affects spermatogenesis and causes DNA alterations in sperm that may lead to chromosome abnormalities in subsequent embryos. Administration of vitamin E before irradiation effectively reduced the frequency of chromosomal abnormalities. The mechanism(s) by which vitamin E reduces genotoxic effects of radiation could be via radical scavenging or antioxidative effects.
The Acetate Switch

SUMMARY To succeed, many cells must alternate between life-styles that permit rapid growth in the presence of abundant nutrients and ones that enhance survival in the absence of those nutrients. One such change in life-style, the “acetate switch,” occurs as cells deplete their environment of acetate-producing carbon sources and begin to rely on their ability to scavenge for acetate. This review explains why, when, and how cells excrete or dissimilate acetate. The central components of the “switch” (phosphotransacetylase [PTA], acetate kinase [ACK], and AMP-forming acetyl coenzyme A synthetase [AMP-ACS]) and the behavior of cells that lack these components are introduced. Acetyl phosphate (acetyl∼P), the high-energy intermediate of acetate dissimilation, is discussed, and conditions that influence its intracellular concentration are described. Evidence is provided that acetyl∼P influences cellular processes from organelle biogenesis to cell cycle regulation and from biofilm development to pathogenesis. The merits of each mechanism proposed to explain the interaction of acetyl∼P with two-component signal transduction pathways are addressed. A short list of enzymes that generate acetyl∼P by PTA-ACKA-independent mechanisms is introduced and discussed briefly. Attention is then directed to the mechanisms used by cells to “flip the switch,” the induction and activation of the acetate-scavenging AMP-ACS. First, evidence is presented that nucleoid proteins orchestrate a progression of distinct nucleoprotein complexes to ensure proper transcription of its gene. Next, the way in which cells regulate AMP-ACS activity through reversible acetylation is described. Finally, the “acetate switch” as it exists in selected eubacteria, archaea, and eukaryotes, including humans, is described.
Liposomal gemcitabine (GemLip)—efficient drug against hormone‐refractory Du145 and PC‐3 prostate cancer xenografts

Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various cancer types (e.g., pancreas) but has only limited effects on hormone‐refractory prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses of Gemc in vitro, the lack of clinical effects might be due to rapid degradation of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa cells. Liposomal formulation (GemLip) is expected to protect the entrapped cytotoxic substance from enzymatic degradation and furthermore augment its accumulation within tumor tissues due to an enhanced permeability of the tumor vessels.
Massage Therapy for Infants and Children

Data are reviewed on the effects of massage therapy on infants and children with various medical conditions. The infants include: premature infants, cocaine-exposed infants, HIV-exposed infants, infants parented by depressed mothers, and full-term infants without medical problems. The childhood conditions include: abuse (sexual and physical), asthma, autism, burns, cancer, developmental delays, dermatitis (psoriasis), diabetes, eating disorders (bulimia), juvenile rheumatoid arthritis, posttraumatic stress disorder, and psychiatric problems. Generally, the massage therapy has resulted in lower anxiety and stress hormones and improved clinical course. Having grandparent volunteers and parents give the therapy enhances their own wellness and provides a cost-effective treatment for the children. J Dev Behav Pediatr 16:105–111. 1994. Index terms: infant massage, massage therapy.
Infrared Pupillometry in Presbyopes Fitted with Soft Contact Lenses

ABSTRACT The influence of pupil size, lens centration, and translation on multifocal contact lens performance suggests that these parameters should be accounted for in the optical design of presbyopic contact lenses. The purpose of the present article is to complete the existing experimental data with clinical measurements of pupil diameter and lens position relative to the pupil in a group of presbyopic, with controlled target luminance, stimulus distance, gaze angle, and convergence. The experiments involve an infrared video-pupillometer and ring-marked contact lenses. Results on pupil aperture show that the effect of changing target distance is comparable in magnitude to that of varying luminance within the photopic range. The measured data on lens position confirm that soft contact lenses are generally decentered from the pupillary axis, usually in inferior temporal direction, and that their average translation between primary and downward gaze is very small. It is also found that the average relative position between lens and pupil centers is slightly modified by changes of luminance in far vision. All these results provide characteristic values which are helpful for the optical modeling of presbyopic contact lenses.
Quantitative analysis of epidermal innervation in Fabry disease

Objective: To use skin biopsy specimens to quantitate the cutaneous innervation density of Fabry patients who had preserved renal function. Background: The small fiber neuropathy of Fabry disease is difficult to detect and quantitate by conventional methods. Because this neuropathy is a common characteristic of Fabry disease, quantitating changes in this parameter would be helpful in demonstrating the effectiveness of enzyme or gene replacement therapy. Methods: Patients underwent skin biopsy at the thigh and foot. Innervation density was determined by counting free nerve endings in the epidermis. These data were compared with nerve conduction studies, and in selected patients, fiber quantitation of sural nerve biopsy specimens. Results: The Fabry patients had normal results of nerve conduction studies and large fiber quantitation by sural nerve biopsy. However, the involvement of small cutaneous fibers in these patients was easily demonstrable and quantifiable by skin biopsy. All patients showed severe loss of intraepidermal innervation at the ankle, but fiber loss at the distal thigh was proportionately less severe. Conclusions: The nerve damage in Fabry patients with preserved renal function involves exclusively small myelinated and unmyelinated fibers, and skin biopsy is a useful in detecting and quantitating such damage. Comparison of cutaneous innervation density with quantitation of sural nerve biopsy specimens demonstrated that skin biopsy specimens were as sensitive in detecting the presence of neuropathy as were the nerve specimens. It is speculated that analysis of cutaneous innervation may provide a useful marker of the nervous system’s response to specific therapy for Fabry disease.
A novel endogenous erythropoietin mediated pathway prevents axonal degeneration

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy. Ann Neurol 2004
Modified screening and ranking algorithm for copy number variation detection

MOTIVATION Copy number variation (CNV) is a type of structural variation, usually defined as genomic segments that are 1 kb or larger, which present variable copy numbers when compared with a reference genome. The screening and ranking algorithm (SaRa) was recently proposed as an efficient approach for multiple change-points detection, which can be applied to CNV detection. However, some practical issues arise from application of SaRa to single nucleotide polymorphism data. RESULTS In this study, we propose a modified SaRa on CNV detection to address these issues. First, we use the quantile normalization on the original intensities to guarantee that the normal mean model-based SaRa is a robust method. Second, a novel normal mixture model coupled with a modified Bayesian information criterion is proposed for candidate change-point selection and further clustering the potential CNV segments to copy number states. Simulations revealed that the modified SaRa became a robust method for identifying change-points and achieved better performance than the circular binary segmentation (CBS) method. By applying the modified SaRa to real data from the HapMap project, we illustrated its performance on detecting CNV segments. In conclusion, our modified SaRa method improves SaRa theoretically and numerically, for identifying CNVs with high-throughput genotyping data. AVAILABILITY AND IMPLEMENTATION The modSaRa package is implemented in R program and freely available at http://c2s2.yale. edu/software/modSaRa. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Circulating Leptin and Adiponectin Concentrations During Tumor Necrosis Factor Blockade in Patients with Active Rheumatoid Arthritis

Objective. Adipocytokines, including leptin and adiponectin, may play an important role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of longterm therapeutic tumor necrosis factor (TNF) blockade on adipocytokine concentrations in patients with RA. Methods. We studied 58 RA patients starting anti-TNF therapy and 58 healthy controls matched for age, sex, and body mass index (BMI). Fasting blood samples were drawn at baseline, 2 weeks, and 6 months after the start of anti-TNF therapy and serum levels of leptin and adiponectin were measured. Results. Patients with RA had increased adiponectin (p < 0.001) and similar leptin concentrations compared with the controls. Leptin concentrations were significantly higher in patients with high BMI (p < 0.001) and correlated positively with BMI at all timepoints (r > 0.75). In contrast, serum adiponectin tended to be higher in lean RA patients and did not correlate with BMI at any timepoint. There were no clear correlations between serum concentrations of adipocytokines and disease activity (Disease Activity Score 28). Short or longterm TNF blockade alone had no influence on circulating leptin and adiponectin concentrations. Patients treated with anti-TNF and concomitant corticosteroids on a stable basis showed a significant decrease in adiponectin levels after 6 months of therapy (p < 0.025). Conclusion. In patients with RA, chronic inflammation and its suppression during anti-TNF therapy have limited influence on plasma leptin concentrations, while significantly decreasing circulating adiponectin levels. Our findings question the suggested key role of inflammatory markers in regulating adipocytokine patterns in RA.
Genotype 3 Diversity and Quantification of Hepatitis E Virus RNA

ABSTRACT Genotype 3 hepatitis E viruses (HEVs) are distributed across the world and are now considered to be an emerging public health concern in industrialized countries. At least 10 genotype 3 subtypes have been identified in humans and animals worldwide. It was recently reported that the sensitivities of HEV RNA assays differ greatly. We have assessed the influence of genotype 3 diversity on the performances of two HEV RNA assays: one targeting the ORF3 gene and the other targeting the ORF2 gene. We tested a panel of 5 HEV-positive reference samples of genotypes 3a, 3b, 3c, 3e, and 3f at 10-fold serial dilutions. The HEV RNA concentrations obtained with both reverse transcription (RT)-PCRs were correlated, but the RT-PCR based on ORF2 underestimated the HEV RNA concentrations. The mean [ORF3 − ORF2] difference was 1.41 log copies/ml. We also tested 34 clinical specimens of genotypes 3c (n = 15), 3e (n = 4), and 3f (n = 15), representing the most prevalent subtypes in Europe. The mean [ORF3 − ORF2] differences were 1.41 log copies/ml for genotype 3c, 0.96 log copies/ml for genotype 3e, and 0.70 log copies/ml for genotype 3f. The bias between the 2 RT-PCR assays was significantly greater for genotype 3c than for genotype 3f (P = 0.007). We therefore recommend the use of an RT-PCR protocol based on ORF3 to quantify HEV RNA of genotype 3 strains.
HIV-related Eye Disease in Patients Presenting to a Tertiary Care Government Hospital in Turkey

Aim: To document the ocular involvement in HIV-infected individuals in Turkey and to compare the findings with those from other centers throughout the world. Methods: In this cross-sectional study, patients with HIV infection being monitored in a tertiary hospital in Istanbul were enrolled. Ocular examination was performed, and the prevalence of ocular manifestations determined. Results: In total, 93 patients were enrolled, of whom 37.6% had ocular pathology. HIV retinopathy was the most frequent retinal finding, affecting 8.6% of the enrolled patients, but none of the affected individuals had any ophthalmic complaints. There were no ocular lesions suggestive of cytomegalovirus (CMV) retinitis. Discussion: In contrast to the case in the developed world, sight-threatening infections are uncommon in Turkish HIV+ patients. The reasons for this are not clear, but it is possible that there are some genetic or environmental protective factors against CMV retinitis in the population studied.