Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity of astroglial responses across human neurodegenerative disorders and brain aging

Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease. Reactive astrocytosis secondary to neuron loss and astrocytopathy due to intrinsic alterations of astrocytes occur in neurodegenerative diseases, overlap each other, and, together with astrocyte senescence, contribute to disease‐specific astrogliopathy in aging and neurodegenerative diseases with abnormal protein aggregates in old age. In addition to the well‐known increase in glial fibrillary acidic protein and other proteins in reactive astrocytes, astrocytopathy is evidenced by deposition of abnormal proteins such as β‐amyloid, hyper‐phosphorylated tau, abnormal α‐synuclein, mutated huntingtin, phosphorylated TDP‐43 and mutated SOD1, and PrPres, in Alzheimer's disease, tauopathies, Lewy body diseases, Huntington's disease, amyotrophic lateral sclerosis and Creutzfeldt‐Jakob disease, respectively. Astrocytopathy in these diseases can also be manifested by impaired glutamate transport; abnormal metabolism and release of neurotransmitters; altered potassium, calcium and water channels resulting in abnormal ion and water homeostasis; abnormal glucose metabolism; abnormal lipid and, particularly, cholesterol metabolism; increased oxidative damage and altered oxidative stress responses; increased production of cytokines and mediators of the inflammatory response; altered expression of connexins with deterioration of cell‐to‐cell networks and transfer of gliotransmitters; and worsening function of the blood brain barrier, among others. Increased knowledge of these aspects will permit a better understanding of brain aging and neurodegenerative diseases in old age as complex disorders in which neurons are not the only players.
Modular transformations of the elliptic hypergeometric functions, Macdonald polynomials, and the shift operator

We consider the space of elliptic hypergeometric functions of the sl_2 type associated with elliptic curves with one marked point. This space represents conformal blocks in the sl_2 WZW model of CFT. The modular group acts on this space. We give formulas for the matrices of the action in terms of values at roots of unity of Macdonald polynomials of the sl_2 type.
SimG: An Alignment Based Method for Evaluating the Similarity of Small Molecules and Binding Sites

In this study, a Gaussian volume overlap and chemical feature based molecular similarity metric was devised, and a downhill simplex searching was carried out to evaluate the corresponding similarity. By representing the shapes of both the candidate small molecules and the binding site with chemical features and comparing the corresponding Gaussian volumes overlaps, the active compounds could be identified. These two aspects compose the proposed method named SimG which supports both structure-based and ligand-based strategies. The validity of the proposed method was examined by analyzing the similarity score variation between actives and decoys as well as correlation among distinct reference methods. A retrospective virtual screening test was carried out on DUD data sets, demonstrating that the performance of structure-based shape matching virtual screening in DUD data sets is substantially dependent on some physical properties, especially the solvent-exposure extent of the binding site: The enrichments of targets with less solvent-exposed binding sites generally exceeds that of the one with more solvent-exposed binding sites and even surpasses the corresponding ligand-based virtual screening.
A Review of the Rationales for Corporate Risk Management: Fashion or the Need?

This paper presents the extensive literature survey based both on theoretical rationales for hedging as well as the empirical evidence that support the implications of the theory regarding the arguments for the corporate risk management relevance and its influence on the company’s value. The survey of literature presented in this paper has revealed that there are two chief classes of rationales for corporate decision to hedge - maximisation of shareholder value or maximisation of managers’ private utility. The paper concludes that, the total benefit of hedging is the combination of all these motives and, if the costs of using corporate risk management instruments are less than the benefits provided via the avenues mentioned in this paper, or any other benefit perceived by the market, then risk management is a shareholder-value enhancing activity.
Comparative Analysis of Toxoplasmosis in Farm Animals by Indirect Hemagglutination Assay and Enzyme linked Immunosorbent Assay

A sero-prevalence survey of Toxoplasmosis in domestic animals (sheep, goats and camels) was conducted in the Najran region of Saudi Arabia from August to November 2014 to determine the status of the disease, as well as to evaluate the diagnostic performance of the serological tests used. A total of 263 sera were tested, 85 sheep; 88 goats and 90 camels, for the presence of Toxoplasma gondii antibodies using Indirect Hemagglutination test (IHAT) and enzyme-linked immunosorbent assay (ELISA). IHAT showed the higher prevalence of Toxoplasmosis (43.5% in sheep flowed by 31.8% in goats and 24.4% in camels) as compared with ELISA. On the other hand, ELISA showed the higher prevalence of Toxoplasmosis in sheep (45.9%) as compared with IHAT(43.5%). When the data from the IHAT was compared with that of the ELISA test, which was used as a reference test for toxoplasmosis, IHAT had the highest sensitivity (88.1%). It could be concluded that the IHAT and ELISA tests are efficient diagnostic tools for detection and selective diagnosis of Toxoplasmosis. Also high seroprevalence of Toxoplasma gondii in studied animals indicated the importance of these animals as the main source of human infection.
Characteristics of bortezomib‐ and thalidomide‐induced peripheral neuropathy

Abstract Dose‐limiting peripheral neuropathy (PN) is frequently reported with the use of thalidomide and bortezomib, novel proteasome inhibitors. While these two agents have significant activity in multiple myeloma (MM), the combination and the associated PN have not been fully examined in untreated patients. The objective of this study was to report the baseline prevalence and occurrence of PN in newly diagnosed MM patients treated with bortezomib and thalidomide. Twenty‐seven patients (11 men and 16 women) with previously untreated MM were prospectively monitored for PN. Total neuropathy score reduced (TNSr) was calculated at baseline and after every two cycles of bortezomib treatment. The median cumulative dose of bortezomib was 35.6 mg/m2 (median 8 cycles) and of thalidomide was 16.8 g. Only three subjects showed mild PN at baseline (whole group median TNSr 0). At the end of treatment, PN developed in 26 patients (median TNSr 8). PN was of mild to moderate severity (TNSr grade 1 = 11, grade 2 = 10, grade 3 = 5, and grade 4 = 0). Nerve conduction studies showed axonal physiology in all except three subjects in whom demyelinating physiology was noted. The median TNSr was 17 in the demyelinating group and 9 in the axonal group. There was no significant correlation of TNSr with cumulative bortezomib or thalidomide dose. At follow‐up, 80% of patients had become asymptomatic after discontinuation of the chemotherapy. We conclude that bortezomib and thalidomide combination chemotherapy induces a reversible length‐dependent sensory>motor, predominantly axonal, large‐fiber>small‐fiber polyneuropathy. In a subset, a more severe demyelinating polyneuropathy may develop.
Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women.

CONTEXT Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. OBJECTIVE The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and women. DESIGN, PARTICIPANTS, AND INTERVENTION In this double-blind, controlled trial, 171 men and women age 50 and older were randomized to receive placebo or 67.5 mmol/d of potassium bicarbonate, sodium bicarbonate, or potassium chloride for 3 months. All subjects received calcium (600 mg of calcium as triphosphate) and 525 IU of vitamin D(3) daily. MAIN OUTCOME MEASURES Twenty-four-hour urinary N-telopeptide and calcium were measured at entry and after 3 months. Changes in these measures were compared across treatment groups in the 162 participants included in the analyses. RESULTS Bicarbonate affected the study outcomes, whereas potassium did not; the two bicarbonate groups and the two no bicarbonate groups were therefore combined. Subjects taking bicarbonate had significant reductions in urinary N-telopeptide and calcium excretion, when compared with subjects taking no bicarbonate (both before and after adjustment for baseline laboratory value, sex, and changes in urinary sodium and potassium; P = 0.001 for both, adjusted). Potassium supplementation did not significantly affect N-telopeptide or calcium excretion. CONCLUSIONS Bicarbonate, but not potassium, had a favorable effect on bone resorption and calcium excretion. This suggests that increasing the alkali content of the diet may attenuate bone loss in healthy older adults.
Inhibition of Malaria Parasite Development by a Cyclic Peptide That Targets the Vital Parasite Protein SERA5

ABSTRACT The serine repeat antigen (SERA) proteins of the malaria parasites Plasmodium spp. contain a putative enzyme domain similar to that of papain family cysteine proteases. In Plasmodium falciparum parasites, more than half of the SERA family proteins, including the most abundantly expressed form, SERA5, have a cysteine-to-serine substitution within the putative catalytic triad of the active site. Although SERA5 is required for blood-stage parasite survival, the occurrence of a noncanonical catalytic triad casts doubt on the importance of the enzyme domain in this function. We used phage display to identify a small (14-residue) disulfide-bonded cyclic peptide (SBP1) that targets the enzyme domain of SERA5. Biochemical characterization of the interaction shows that it is dependent on the conformation of both the peptide and protein. Addition of this peptide to parasite cultures compromised development of late-stage parasites compared to that of control parasites or those incubated with equivalent amounts of the carboxymethylated peptide. This effect was similar in two different strains of P. falciparum as well as in a transgenic strain where the gene encoding the related serine-type parasitophorous vacuole protein SERA4 was deleted. In compromised parasites, the SBP1 peptide crosses both the erythrocyte and parasitophorous vacuole membranes and accumulates within the parasitophorous vacuole. In addition, both SBP1 and SERA5 were identified in the parasite cytosol, indicating that the plasma membrane of the parasite was compromised as a result of SBP1 treatment. These data implicate an important role for SERA5 in the regulation of the intraerythrocytic development of late-stage parasites and as a target for drug development.
Inferior Interatrial Pathway in the Dog

In 20 anesthetized dogs, close bipolar electrograms consisting of two deflections were recorded along the ligament of Marshall in the posterior left atrium. At the inferior portion of the ligament the deflections were separated by an interval of 10−15 msec and at the level of the left superior pulmonary vein by an interval of 60 msec or more. Histological and electrophysiological studies indicated that both deflections were associated with striated cardiac muscle; the first deflection was designated as a left atrial muscle potential and the second as a left atrial tract potential. Although the left atrial muscle potential was coincident with the middle portion of the P wave, the left atrial tract potential occurred during some part of the P-R segment. Conduction to the left atrial tract potential was altered, delayed, or completely blocked during retrograde conduction in the atrium, rapid pacing of the atrium (300−500/min), or local cooling at the point where the ligament of Marshall joined the inferior left atrium near the origin of the coronary sinus. Crushing Bachmann's bundle caused delay in conduction to the left atrial muscle but not to the left atrial tract. Left cardiac sympathetic nerve stimulation induced an atrial activation pattern consistent with pacemaker activity in the inferior left atrium, with inversion of the P wave in lead II. Pacing from the edge of the ligament of Marshall in the posterior left atrium produced the same change in P-wave morphology. These data indicate that the left atrial tract represents a terminal, insulated tract which is activated through an inferior interatrial pathway connecting the inferior right and left atria along the coronary sinus. The terminal end of the tract showed no reinsertion into atrial musculature.
Recovery of Adrenal Function after Long-Term Glucocorticoid Therapy for Giant Cell Arteritis: A Cohort Study

Objectives Giant cell arteritis (GCA) is a chronic systemic vasculitis of large and medium-sized arteries, for which long-term glucocorticoid (GC) treatment is needed. During GC withdrawal patients can suffer adrenal insufficiency. We sought to determine the time until recovery of adrenal function after long-term GC therapy, and to assess the prevalence and predictors for secondary adrenal insufficiency. Subjects and Design 150 patients meeting the ACR criteria for GCA between 1984 and 2012 were analyzed. All received the same GC treatment protocol. The low-dose ACTH stimulation test was repeated annually until adrenal recovery. Biographical, clinical and laboratory data were collected prospectively and compared. Results At the first ACTH test, 74 (49%) patients were non-responders: of these, the mean time until recovery of adrenal function was 14 months (max: 51 months). A normal test response occurred within 36 months in 85% of patients. However, adrenal function never recovered in 5% of patients. GC of >15 mg/day at 6 months, GC of >9.5 mg/day at 12 months, treatment duration of >19 months, a cumulative GC dose of >8.5 g, and a basal cortisol concentration of <386 nmol/L were all statistically associated with a negative response in the first ACTH test (p <0.05). Conclusion Adrenal insufficiency in patients with GCA, treated long-term with GC, was frequent but transitory. Thus, physicians’ vigilance should be increased and an ACTH test should be performed when GC causes the above associated statistical factors.
Computational Modeling of the Time-dependent Behavior of Cementitious Materials

i i DEDICATION . iii ACKNOWLEDGEMENTS . iv CONTRIBUTORS AND FUNDING SOURCES . v TABLE OF CONTENTS . vi LIST OF FIGURES . ix 1. BACKGROUND AND OBJECTIVES . 1 1.1 Motivation and problem statement . 1 1.2 Objectives . 4 1.3 Disposition . 5 2. COMPUTATIONALLY IMPLEMENTED MODEL . 7 2.1 Conceptualization and kinematic framework . 7 2.2 Computational implementation . 19 2.2.1 Microstructural modeling . 19 2.2.2 Finite element calculation . 21 2.2. 3 Logic flow of the computational scheme . 28 2.2. 4 Model validation . 31 3. CREEP/RELAXATION CAUSED BY C-S-H VISCOELASTICITY AND C-S-H AGING . 35 3.1 Intrinsic C-S-H viscoelasticity . 35 3.2 C-S-H aging . 38 3.2.1 C-S-H aging implementation . 38 3.2.2 Simulation results & discussions . 41 3.3 Summary . 51 4. CREEP/RELAXATION CAUSED BY CEMENT GRAIN DISSOLUTION . 52 4.1 Cement grain dissolution . 52 4.1.1 Different loading ages . 53 4.1.2 Different w/c . 54 vii 4.1.3 Evolution of stresses . 56 4.2 Comparison with solidification theory . 58 4.3 Summary . 61 5. EVOLUTION OF APPARENT VE/VP POISSON’S RATIO CAUSED BY BOTH INTRINSIC C-S-H CREEP AND CEMENT GRAIN DISSOLUTION . 63 5.1 Definition of VE/VP Poisson’s ratio . 63 5.2 Simulation results & discussions . 65 5.2.1 Poisson’s Ratio evolution due to cement grain dissolution . 68 5.2.2 Poisson’s Ratio evolution due to intrinsic C-S-H viscoelasticity . 74 5.2. 3 Poisson’s Ratio evolution due to simultaneous intrinsic C-S-H relaxation and cement grain dissolution . 81 5.3 Summary . 87 6. EARLY AGE DESICCATION SHRINKAGE CAUSED BY BOTH INTRINSIC C-S-H CREEP AND CEMENT GRAIN DISSOLUTION . 88 6.1 Background of desiccation shrinkage . 88 6.2 Shrinkage prediction implementation . 90 6.3 Simulation results & discussions . 93 6.3.1 Different ages of drying . 94 6.3.2 Different w/c . 95 6.3.3 Time-evolving RH . 96 6.3. 4 Recovering RH . 101 6.3. 5 Cyclic drying and rewetting . 102 6.3. 6 Combined irreversibility due to dissolution and intrinsic plasticity . 106 6.4 Summary . 111 7. CREEP/RELAXATION CAUSED BY STRESS-INDUCED DISSOLUTION . 112 7.1 Background of stress-induced dissolution . 112 7.2 Conceptualization . 114 7.2.1 Thermodynamic framework . 114 7.2.2 Dissolution kinetics . 118 7.3 Computational implementation . 121 7.3.1 Computational implementation . 121 7.3.2 Choice of thermodynamic equilibrium domain size . 129 7.4 Simulation results and discussions . 135 7.4.1 Different choices of domain size . 135 7.4.2 Stochastic microstructures of cement paste. 143 7.4.3 Different magnitudes of applied strain/stress . 145 7.4. 4 C-S-H and CH dissolution . 147 7.4. 5 Different w/c . 150 viii 7.4. 6 Different loading ages . 152 7.5 Summary . 153 8. CONCLUSIONS . 154 8.1 Dissertation summary and primary conclusions . 154 8.2 Limitations of the computational model and future research . 156 REFERENCES . 158
Clinical Outcomes Using a Platelet Function-Guided Approach for Secondary Prevention in Patients With Ischemic Stroke or Transient Ischemic Attack

Background and Purpose— Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. Methods— From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. Aspirin nonresponse was defined as a mean platelet aggregation ≥20% with 0.5 mg/mL arachidonic acid and/or ≥70% with 5 &mgr;mol/L adenosine diphosphate. Clopidogrel nonresponse was defined as a mean platelet aggregation ≥40% with 5 &mgr;mol/L adenosine diphosphate. A modification was any increase in antiplatelet therapy occurring after testing. Clinical outcomes were compared between patients with and without platelet function-guided antiplatelet therapy modifications using univariate and propensity score-adjusted analyses. Results— In patients with ischemic stroke or transient ischemic attack, 43% (n=128) and 35% (n=54) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 23% of patients (n=73). After propensity score matching (n=61 in each group), antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard ratio, 2.24; 95% CI, 1.12–4.47; P=0.02) compared with no modification in antiplatelet therapy and a trend toward increased bleeding (hazard ratio, 3.56; 95% CI, 0.98–12.95; P=0.05). No differences in ischemic events were observed. Conclusions— Platelet function-guided modification in antiplatelet therapy after an ischemic stroke or transient ischemic attack was associated with significantly higher rates of adverse clinical outcomes.
Comment on ‘Fast attainment of computer cursor control with noninvasively acquired brain signals’

In a recent paper by Bradberry, Gentili and Contreras-Vidal published in Journal of Neural Engineering (2011, 8 036010), an interesting method for the control of a two-dimensional mouse cursor was proposed, which apparently attained excellent control and good speed with relatively simple techniques. We believe some of the results in the paper have been misinterpreted due to a failure in appreciating the self-fulfilling nature of the success criteria adopted. In this comment, we explain the nature of the problem and attempt to assess its influence on the results reported in the aforementioned paper.
Factors affecting the adoption of healthcare information technology

In order to improve the quality and performance of healthcare services, healthcare information technology is among the most important technology in healthcare supply chain management. This study sets out to apply and test the Unified Theory of Acceptance and Use of Technology (UTAUT), to examine the factors influencing healthcare Information Technology (IT) services. A structured questionnaire was developed and distributed to healthcare representatives in each province surveyed in Thailand. Data collected from 400 employees including physicians, nurses, and hospital staff members were tested the model using structural equation modeling technique. The results found that the factors with a significant effect are performance expectancy, effort expectancy and facilitating conditions. They were also found to have a significant impact on behavioral intention to use the acceptance healthcare technology. In addition, in Thai provincial areas, positive significance was found with two factors: social influence on behavioral intention and facilitating conditions to direct using behavior. Based on research findings, in order for healthcare information technology to be widely adopted and used by healthcare staffs in healthcare supply chain management, the healthcare organizational management should improve healthcare staffs' behavioral intention and facilitating conditions.
Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso‐occlusive crises in patients with sickle cell disease: a phase III randomized, placebo‐controlled, double‐blind study of the gardos channel blocker senicapoc (ICA‐17043)

Red blood cell (RBC) hydration is regulated in part by the Ca2+‐activated K+ efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo‐controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty‐five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.