Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a Highly Sensitive Cytotoxicity Assay System for CYP3A4-Mediated Metabolic Activation

Drug-induced hepatotoxicity, which is a rare but serious adverse reaction to a large number of pharmaceutical drugs, is sometimes associated with reactive metabolites produced by drug-metabolizing enzymes. In the present study, we constructed a cell-based system to evaluate the cytotoxicity of reactive metabolites produced by CYP3A4 using human hepatoma cells infected with an adenovirus vector expressing human CYP3A4 (AdCYP3A4). When seven hepatoma cell lines (HepG2, Hep3B, HLE, HLF, Huh6, Huh7, and Fa2N4 cells) were infected with AdCYP3A4, HepG2 cells showed the highest CYP3A4 protein expression and testosterone 6β-hydroxylase activity (670 pmol · min−1 · mg−1). With the use of AdCYP3A4-infected HepG2 cells, the cytotoxicities of 23 drugs were evaluated by the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, and the cell viability when treated with 11 drugs (amiodarone, desipramine, felbamate, isoniazid, labetalol, leflunomide, nefazodone, nitrofurantoin, tacrine, terbinafine, and tolcapone) was significantly decreased. Moreover, the transfection of siRNA for nuclear factor erythroid 2-related factor 2 (Nrf2) to decrease the cellular expression level of Nrf2 exacerbated the cytotoxicity of some drugs (troglitazone, flutamide, acetaminophen, clozapine, terbinafine, and desipramine), suggesting that the genes regulated by Nrf2 are associated with the detoxification of the cytotoxicities mediated by CYP3A4. We constructed a highly sensitive cell-based system to detect the drug-induced cytotoxicity mediated by CYP3A4. This system would be beneficial in preclinical screening in drug development and increase our understanding of the drug-induced cytotoxicity associated with CYP3A4.
Morbillivirus-associated unusual mortality event in South Australian bottlenose dolphins is largest reported for the Southern Hemisphere

Cases of morbillivirus have been recorded in the Southern Hemisphere but have not been linked to significant marine mammal mortality. Post-mortems were conducted on 58 carcasses (44 Indo-Pacific bottlenose dolphins, two common bottlenose dolphins, 12 short-beaked common dolphins) from South Australia during 2005–2013, including an unusual mortality event (UME) in St Vincent Gulf Bioregion (SVG) during 2013. Diagnostic pathology, circumstance of death, body condition, age and stomach contents were documented for Indo-Pacific bottlenose dolphins. At least 50 dolphins died during the UME, 41 were Indo-Pacific bottlenose dolphins and most were young. The UME lasted about seven months and had two peaks, the first being the largest. Effect on the population is unknown. Diagnostic testing for morbillivirus was conducted on 57 carcasses, with evidence for infection in all species during 2011–2013. All tested UME bottlenose dolphins were positive for cetacean morbillivirus (CeMV), and the pathology included interstitial pneumonia, lymphoid depletion and syncytia. Concurrent pathologies, including lung parasite and fungal infections, and severe cutaneous bruising were observed in many dolphins. The event coincided with elevated water temperatures, a diatom bloom and significant fish die-offs. We conclude that the cause for the UME was multifactorial and that CeMV was a major contributor.
Preliminary Study on the Expression and the Clinical Significance of CD133 in Peripheral Blood of Patients with Gastric Adenocarcinoma

Background. Significances of CD133 mRNA in peripheral blood mononuclear cells (PBMCs) of gastric adenocarcinoma (GC) patients were investigated. Methods. Correlations of CD133 mRNA expression in PBMCs on clinicopathological parameters or CD133 protein expression were analyzed. Receiver operating characteristic curve according to bright scale value (BSV) of CD133 mRNA was used to group patients for prognosis analysis. Results. BSV of preoperative CD133 mRNA in PBMCs in GC was significantly higher than that in volunteers or in GU. Invasive depth or metastatic lymph node number for higher BSV of preoperative CD133 mRNA and invasive depth or lymphatic vessel invasion for higher BSV of postoperative CD133 mRNA in the PBMCs were identified. Patients with CD133+ expression in primary lesion had a significantly higher expression of preoperative CD133 mRNA in the PBMCs. The expression of preoperative or postoperative CD133 mRNA in PBMCs related positively to CD133 mRNA expression in primary lesion. Patients with higher expression of preoperative or postoperative CD133 mRNA shared significantly shorter survival compared with that in lower expression group. Conclusion. Higher levels of preoperative or postoperative CD133 mRNA in PBMCs of GC correlated positively to the lymphatic metastasis and the BSV of CD133 mRNA in primary lesion, indicating the poorer survival.
Memory Avoidance by Older Adults

Learning often involves a transition from responding based on an effortful initial strategy to using a faster and easier memory-based strategy. Older adults shift strategy more slowly compared with younger adults. I describe research establishing that age differences in strategy shift are impacted not only by declines in older adults’ learning but also by their volitional avoidance of memory retrieval. I also discuss the factors that influence older adults’ memory avoidance, including their understanding of the available strategies’ relative efficiency, accuracy, and effortfulness, as well as age differences in the preference for a consistent strategic approach. Last, I consider the implications of memory avoidance for older adults’ everyday functioning. This research demonstrates that volition and choice must be taken into account when studying cognitive performance and aging.
Visual Anticipatory Information Modulates Multisensory Interactions of Artificial Audiovisual Stimuli

The neural activity of speech sound processing (the N1 component of the auditory ERP) can be suppressed if a speech sound is accompanied by concordant lip movements. Here we demonstrate that this audiovisual interaction is neither speech specific nor linked to humanlike actions but can be observed with artificial stimuli if their timing is made predictable. In Experiment 1, a pure tone synchronized with a deformation of a rectangle induced a smaller auditory N1 than auditory-only presentations if the temporal occurrence of this audiovisual event was made predictable by two moving disks that touched the rectangle. Local autoregressive average source estimation indicated that this audiovisual interaction may be related to integrative processing in auditory areas. When the moving disks did not precede the audiovisual stimulus—making the onset unpredictable—there was no N1 reduction. In Experiment 2, the predictability of the leading visual signal was manipulated by introducing a temporal asynchrony between the audiovisual event and the collision of moving disks. Audiovisual events occurred either at the moment, before (too “early”), or after (too “late”) the disks collided on the rectangle. When asynchronies varied from trial to trial—rendering the moving disks unreliable temporal predictors of the audiovisual event—the N1 reduction was abolished. These results demonstrate that the N1 suppression is induced by visual information that both precedes and reliably predicts audiovisual onset, without a necessary link to human action-related neural mechanisms.
Fast Asynchronous Uniform Consensus in Real-Time Distributed Systems

We investigate whether asynchronous computational models and asynchronous algorithms can be considered for designing real-time distributed fault-tolerant systems. A priori, the lack of bounded finite delays is antagonistic with timeliness requirements. We show how to circumvent this apparent contradiction, via the principle of "late binding" of a solution to some (partially) synchronous model. This principle is shown to maximize the coverage of demonstrated safety, liveness, and timeliness properties. These general results are illustrated with the uniform consensus (UC) and real-time UC problems, assuming processor crashes and reliable communications, considering asynchronous solutions based upon unreliable failure detectors. We introduce the concept of fast failure detectors and show that the problem of building strong or perfect fast failure detectors in real systems can be stated as a distributed message scheduling problem. A generic solution to this problem is given and illustrated considering deterministic Ethernets. In passing, it is shown that, with our construction of unreliable failure detectors, asynchronous algorithms that solve UC have a worst-case termination lower bound that matches the optimal synchronous lower bound. Finally, we introduce FastUC, a novel solution to UC, that is based upon fast failure detectors.
Binary Regression in Truncated Samples, with Application to Comparing Dietary Instruments in a Large Prospective Study

Summary We examine two issues of importance in nutritional epidemiology: the relationship between dietary fat intake and breast cancer, and the comparison of different dietary assessment instruments, in our case the food frequency questionnaire (FFQ) and the multiple‐day food record (FR). The data we use come from women participants in the control group of the Dietary Modification component of the Women's Health Initiative (WHI) Clinical Trial. The difficulty with the analysis of this important data set is that it comes from a truncated sample, namely those women for whom fat intake as measured by the FFQ amounted to 32% or more of total calories. We describe methods that allow estimation of logistic regression parameters in such samples, and also allow comparison of different dietary instruments. Because likelihood approaches that specify the full multivariate distribution can be difficult to implement, we develop approximate methods for both our main problems that are simple to compute and have high efficiency. Application of these approximate methods to the WHI study reveals statistically significant fat and breast cancer relationships when a FR is the instrument used, and demonstrate a marginally significant advantage of the FR over the FFQ in the local power to detect such relationships.
Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries.

BACKGROUND Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. OBJECTIVE This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. METHODS This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. RESULTS For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. CONCLUSION Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.
Random Multi-Constraint Projection: Stochastic Gradient Methods for Convex Optimization with Many Constraints

Consider convex optimization problems subject to a large number of constraints. We focus on stochastic problems in which the objective takes the form of expected values and the feasible set is the intersection of a large number of convex sets. We propose a class of algorithms that perform both stochastic gradient descent and random feasibility updates simultaneously. At every iteration, the algorithms sample a number of projection points onto a randomly selected small subsets of all constraints. Three feasibility update schemes are considered: averaging over random projected points, projecting onto the most distant sample, projecting onto a special polyhedral set constructed based on sample points. We prove the almost sure convergence of these algorithms, and analyze the iterates' feasibility error and optimality error, respectively. We provide new convergence rate benchmarks for stochastic first-order optimization with many constraints. The rate analysis and numerical experiments reveal that the algorithm using the polyhedral-set projection scheme is the most efficient one within known algorithms.
Employment and the associated impact on quality of life in people diagnosed with schizophrenia

A systematic review was conducted to assess the employment rate of people with schizophrenia. Additionally, information from the selected studies concerning factors associated with employment and health-related quality of life (HRQoL) was examined. Employment rates ranged from 4% to 50.4%. The studies differed considerably in design, patient settings, and methods of recruitment. The most frequently reported factors associated with employment were negative and cognitive symptoms, age of onset, and duration and course of the disease. Individual characteristics associated with unemployment were older age, lower education, and sex (female). Additionally, environmental factors, eg, the availability of welfare benefits and vocational support programs, seemed to play a role. Generally, being employed was positively associated with HRQoL. However, the causal direction of this association remained unclear, as studies on the bidirectional relationship between employment and HRQoL were lacking.
Proteomic and Immunoblot Analyses of Bartonella quintana Total Membrane Proteins Identify Antigens Recognized by Sera from Infected Patients

ABSTRACT Bartonella quintana is a fastidious, gram-negative, rod-shaped bacterium that causes prolonged bacteremia in immunocompetent humans and severe infections in immunocompromised individuals. We sought to define the outer membrane subproteome of B. quintana in order to obtain insight into the biology and pathogenesis of this emerging pathogen and to identify the predominant B. quintana antigens targeted by the human immune system during infection. We isolated the total membrane proteins of B. quintana and identified 60 proteins by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and peptide mass fingerprinting. Using the newly constructed proteome map, we then utilized two-dimensional immunoblotting with sera from 21 B. quintana-infected patients to identify 24 consistently recognized, immunoreactive B. quintana antigens that have potential relevance for pathogenesis and diagnosis. Among the outer membrane proteins, the variably expressed outer membrane protein adhesins (VompA and VompB), peptidyl-prolyl cis-trans-isomerase (PpI), and hemin-binding protein E (HbpE) were recognized most frequently by sera from patients, which is consistent with surface expression of these virulence factors during human infection.
Relationship between Soft Drink Consumption and Obesity in 9–11 Years Old Children in a Multi-National Study

The purpose of this study was to determine the association between regular (sugar containing) and diet (artificially sweetened) soft drink consumption and obesity in children from 12 countries ranging in levels of economic and human development. The sample included 6162 children aged 9–11 years. Information on soft drink consumption was obtained using a food frequency questionnaire. Percentage body fat (%BF) was estimated by bio-electrical impedance analysis, body mass index (BMI) z-scores were computed using World Health Organization reference data, and obesity was defined as a BMI > +2 standard deviations (SD). Multi-level models were used to investigate trends in BMI z-scores, %BF and obesity across categories of soft drink consumption. Age, sex, study site, parental education and physical activity were included as covariates. There was a significant linear trend in BMI z-scores across categories of consumption of regular soft drinks in boys (p = 0.049), but not in girls; there were no significant trends in %BF or obesity observed in either boys or girls. There was no significant linear trend across categories of diet soft drink consumption in boys, but there was a graded, positive association in girls for BMI z-score (p = 0.0002) and %BF (p = 0.0001). Further research is required to explore these associations using longitudinal research designs.
Detection of Microorganisms in Granulomas That Have Been Formalin-Fixed: Review of the Literature Regarding Use of Molecular Methods

Granuloma is an organized aggregate of immune cells that under the microscope appear as epithelioid macrophages. A granuloma can only be diagnosed when a pathologist observes this type of inflammation under the microscope. If a foreign body or a parasite is not observed inside the granuloma, stains for acid-fast bacilli and fungi are ordered since mycobacteria and fungi are frequently the cause of this type of inflammation. It is calculated that 12 to 36% of granulomas do not have a specific etiology and many have wondered if with new molecular methods we could reduce this number. This paper will summarize the frequently known causes of granulomas and will present the recent literature regarding the use of molecular techniques on tissue specimens and how these have helped in defining causative agents. We will also briefly describe new research regarding formation and function of granulomas and how this impacts our ability to find an etiologic agent.
Inhibition of heparin-binding epidermal growth factor-like growth factor increases albuminuria in puromycin aminonucleoside nephrosis.

BACKGROUND Our previous work in the acute puromycin aminonucleoside nephrosis (PAN) model has demonstrated up-regulation of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA and protein within glomerular epithelial cells (GECs) prior to the onset of proteinuria. METHODS To determine whether increased HB-EGF expression in the acute PAN model contributes to the pathogenesis of proteinuria, a monoclonal antibody (DE10) was produced against recombinant human HB-EGF. RESULTS The specificity of DE10 for human HB-EGF was confirmed by enzyme-linked immunosorbent assay, immunohistochemical staining, and flow cytometry of transfected cells expressing human and rat HB-EGF, and inhibition of cell proliferation. DE10 also reacted with cells transfected with rat HB-EGF cDNA. Administration of 0.5 mg affinity-purified DE10 to normal rats did not cause significant albuminuria compared with controls. Five days after the induction of the acute PAN model, albuminuria was significantly greater in animals treated with 0.5 mg DE10 than a control mAb (162.6 +/- 32.4 vs. 64.8 +/- 10.2 mg/day, respectively, P < 0.01). Rats treated with DE10 had an earlier onset of severe albuminuria, but no increase in maximal albuminuria at later time points. Electron microscopy showed marked podocyte effacement in both DE10-treated and control animals, but no obvious difference between groups. However, adhesion of the human GEC line 56/10 A1 to laminin and fibronectin, but not to collagens I or IV, was reduced by DE10. CONCLUSIONS This study suggests that HB-EGF contributes to the integrity of the glomerular filtration barrier, particularly when the podocyte has been injured. Following podocyte injury, adhesion to laminin in the glomerular basement membrane by HB-EGF may be important in reducing albuminuria.
Multivariate $p$-adic formal congruences and integrality of Taylor coefficients of mirror maps

We generalise Dwork's theory of $p$-adic formal congruences from the univariate to a multi-variate setting. We apply our results to prove integrality assertions on the Taylor coefficients of (multi-variable) mirror maps. More precisely, with $\mathbf z=(z_1,z_2,.,z_d)$, we show that the Taylor coefficients of the multi-variable series $q(\mathbf z)=z_i\exp(G(\mathbf z)/F(\mathbf z))$ are integers, where $F(\mathbf z)$ and $G(\mathbf z)+\log(z_i) F(\mathbf z)$, $i=1,2,. ,d$, are specific solutions of certain GKZ systems. This result implies the integrality of the Taylor coefficients of numerous families of multi-variable mirror maps of Calabi-Yau complete intersections in weighted projective spaces, as well as of many one-variable mirror maps in the "Tables of Calabi-Yau equations" [arXiv:math/0507430] of Almkvist, van Enckevort, van Straten and Zudilin. In particular, our results prove a conjecture of Batyrev and van Straten in [Comm. Math. Phys. 168 (1995), 493-533] on the integrality of the Taylor coefficients of canonical coordinates for a large family of such coordinates in several variables.
Velocity Distribution and Intimal Proliferation in Autologous Vein Grafts in Dogs

SUMMARY Autologous femoral veins grafted between the external iliac arteries in 18 dogs provided a model for studying the hemodynamics and histopathology of vein graft bypasses. The angle of proximal anastomosis was varied by groups (<90°, 90°, >90°) to produce a wide range of flow conditions within the grafts. Four months after implantation, point velocity measurements of blood flow and histological examination of the superior and inferior walls were made at proximal, middle, and distal locations in each graft. Hot-film velocity measurements revealed outwardly skewed velocity profiles in the proximal locations in all grafts, and flow visualization models showed secondary fluid motions and separation zones at those regions. Velocity profiles in the middle and distal regions of the grafts were more symmetrical and showed no flow separation. Histological examination of wall sections along the graft length showed that intimal proliferation occurred focally and ranged from 1 to 100 fita in thickness. No signficant correlation between graft angle and degree of intimal proliferation was found. However, there was a weak inverse correlation between the apparent fluid shear rate and the corresponding degree of intimal proliferation, with the greatest proliferation occurring in the regions experiencing the lowest shearing forces. Regions of low shear rate should be avoided by maintaining adequate flow rates through the grafts and thus minimising losses of patency due to both thrombus formation and intimal proliferation.