Miracle-dz/UniFAR-FTUs huggingface dataset:
On the equivalence of global quadratic growth condition and second-order sufficient condition

The main purpose of this thesis is to study various properties of quadratically constrained quadratic programming problems. We concentrate on the existence of solutions and global second-order sufficient conditions for the quadratic problems. First, we study the existence of global solutions for general quadratic programming problems. With the tool of asymptotical directions of sets, we provide an alternative proof for the nonemptiness of intersection of a sequence of nested sets defined by a finite number of convex quadratic functions, which can be applied to show the existence results of the corresponding optimization problems. We also prove the existence of global solutions of the convex quadratic program with convex quadratic constraints by an analytic approach. Next, we study the global quadratic growth condition and the global second-order sufficient condition for the quadratic programming problems. By formulating the problem in the form of minimizing a maximum function of a finite number of quadratic functions, we study the relation between the global quadratic growth condition and the global second-order sufficient condition for the maximum function. As is shown, the global second-order sufficient condition implies the global quadratic growth condition. But the reverse implication is in general not true. We show that, when the solution set is a singleton and the number of quadratic term is 2, the reverse implication holds. For the homogeneous quadratic case, these two are equivalent. We then apply the corresponding results to the constrained optimization problem in standard form. Finally, we investigate the fractional programming problems. We present the Slemma for the fractional functions. We also obtain the attainability property of various types of fractional programming problems.
Plasmodium falciparum GAP40 Plays an Essential Role in Merozoite Invasion and Gametocytogenesis

Red blood cell invasion is central to the pathogenesis of the malaria parasite, and the parasite proteins involved in this process are potential therapeutic targets. Gliding motility powers merozoite invasion and is driven by a unique molecular motor termed the glideosome. ABSTRACT Cyclic invasion of red blood cells (RBCs) by Plasmodium merozoites is associated with the symptoms and pathology of malaria. Merozoite invasion is powered actively and rapidly by a parasite actomyosin motor called the glideosome. The ability of the glideosome to generate force to support merozoite entry into the host RBCs is thought to rely on its stable anchoring within the inner membrane complex (IMC) through membrane-resident proteins, such as GAP50 and GAP40. Using a conditional knockdown (KD) approach, we determined that PfGAP40 was required for asexual blood-stage replication. PfGAP40 is not needed for merozoite egress from host RBCs or for the attachment of merozoites to new RBCs. PfGAP40 coprecipitates with PfGAP45 and PfGAP50. During merozoite invasion, PfGAP40 is associated strongly with stabilizing the expression levels of PfGAP45 and PfGAP50 in the schizont stage. Although PfGAP40 KD did not influence IMC integrity, it impaired the maturation of gametocytes. In addition, PfGAP40 is phosphorylated, and mutations that block phosphorylation of PfGAP40 at the C-terminal serine residues S370, S372, S376, S405, S409, S420, and S445 reduced merozoite invasion efficiency. Overall, our findings implicate PfGAP40 as an important regulator for the gliding activity of merozoites and suggest that phosphorylation is required for PfGAP40 function. IMPORTANCE Red blood cell invasion is central to the pathogenesis of the malaria parasite, and the parasite proteins involved in this process are potential therapeutic targets. Gliding motility powers merozoite invasion and is driven by a unique molecular motor termed the glideosome. The glideosome is stably anchored to the parasite inner membrane complex (IMC) through membrane-resident proteins. In the present study, we demonstrate the importance of an IMC-resident glideosome component, PfGAP40, that plays a critical role in stabilizing the expression levels of glideosome components in the schizont stage. We determined that phosphorylation of PfGAP40 at C-terminal residues is required for efficient merozoite invasion.
Exploring Chronic Pain and Pain Management Perspectives: Qualitative Pilot Analysis of Web-Based Health Community Posts

Background Patient perspectives are central to the US Food and Drug Administration’s benefit-risk decision-making process in the evaluation of medical products. Traditional channels of communication may not be feasible for all patients and consumers. Social media websites have increasingly been recognized by researchers as a means to gain insights into patients’ views about treatment and diagnostic options, the health care system, and their experiences living with their conditions. Consideration of multiple patient perspective data sources offers the Food and Drug Administration the opportunity to capture diverse patient voices and experiences with chronic pain. Objective This pilot study explores posts from a web-based patient platform to gain insights into the key challenges and barriers to treatment faced by patients with chronic pain and their caregivers. Methods This research compiles and analyzes unstructured patient data to draw out the key themes. To extract relevant posts for this study, predefined keywords were identified. Harvested posts were published between January 1, 2017, and October 22, 2019, and had to include #ChronicPain and at least one other relevant disease tag, a relevant chronic pain management tag, or a chronic pain management tag for a treatment or activity specific to chronic pain. Results The most common topics discussed among persons living with chronic pain were related to disease burden, the need for support, advocacy, and proper diagnosis. Patients’ discussions focused on the negative impact chronic pain had on their emotions, playing sports, or exercising, work and school, sleep, social life, and other activities of daily life. The 2 most frequently discussed treatments were opioids or narcotics and devices such as transcutaneous electrical nerve stimulation machines and spinal cord stimulators. Conclusions Social listening data may provide valuable insights into patients’ and caregivers’ perspectives, preferences, and unmet needs, especially when conditions may be highly stigmatized.
Cytoprotective Properties of Citronella Oil (Cymbopogon nardus (L.) Rendl.) and Lemongrass Oil (Cymbopogon citratus (DC.) Stapf) through Attenuation of Senescent-Induced Chemotherapeutic Agent Doxorubicin on Vero and NIH-3T3 Cells

Objective: This study aimed to determine the cytoprotective potentials of citronella (Cymbopogon nardus (L.) Rendl. ) essential oil (CO) and lemongrass (Cymbopogon citratus (DC.) Stapf) essential oil (LO). Methods: The essential oils from citronella and lemongrass were obtained by steam-water distillation, then analyzed using Gas Chromatography-Mass Spectrophotometry (GC-MS) to determine the chemical constituents. The antioxidant activity of CO and LO was compared using a total antioxidant capacity kit. The viability of normal kidney epithelial cells Vero and fibroblast NIH-3T3 as the cell models were tested using a trypan blue exclusion assay. The effect of cellular senescence inhibition on both cell models was measured using senescence-associated β-galactosidase (SA-β-gal) staining. The mechanism of action of CO and LO in the protection of cellular damage against doxorubicin was also confirmed through 2’,7’–dichlorofluorescin diacetate (DCFDA) staining to discover the ability to decrease reactive oxygen species (ROS) levels and a gelatin zymography assay to observe the activity of matrix metalloproteinases (MMPs). Results: The major marker components of CO and LO were citronellal and citral, respectively. Both oils showed low cytotoxic activity against Vero and NIH-3T3 cells, with IC50 values of over 40 µg/mL. LO exhibited higher antioxidant capacity than CO, but there was no effect on the intracellular ROS level of both oils on Vero and NIH-3T3 cells. However, CO and LO decreased cellular senescence induced by doxorubicin exposure on both cells, as well as suppressed MMP-2 expression. Conclusion: Both CO and LO decrease the cellular senescence and MMP-2 expression with less cytotoxic effects on normal cells independently from their antioxidant capacities. The results were expected to support the use of CO and LO as tissue protective and anti-aging agents in maintaining the body’s cellular health against chemotherapeutics or cellular damaging agents.
Light absorption and plasmon – exciton interaction in three-layer nanorods with a gold core and outer shell composed of molecular J- and H-aggregates of dyes

Optical properties of hybrid rod-like nanoparticles, consisting of a gold core, an intermediate passive organic layer (spacer) and outer layer of ordered molecular cyanine dye aggregates, are experimentally and theoretically investigated. It is shown that these dyes can form not only ordered J-aggregates but also H-aggregates (differing by the packing angle of dye molecules in an aggregate and having other spectral characteristics) in the outer shell of the hybrid nanostructure. Absorption spectra of synthesised three-layer nanorods are recorded, and their sizes are determined. The optical properties of the composite nanostructures under study are found to differ significantly, depending on the type of the molecular aggregate formed in the outer shell. The experimental data are quantitatively explained based on computer simulation using the finite-difference time-domain (FDTD) method, and characteristic features of the plasmon – exciton interaction in the systems under study are revealed.
Epidemiology of Lung Cancer in Kazakhstan: Trends and Geographic Distribution

Objective: The aim is to study the trends of lung cancer (LC) incidence in the regional context in Kazakhstan. Methods: The retrospective study was done using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in sanitary statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period. Results: Over the 10 years under study, 36,916 new cases of LC were registered in the country (80.5% – in men and 19.5% – in women). During the studied years the average age of patients was 64.2±0.1 years (95%CI=63.9-64.4). The highest incidence rates per 100,000 in the entire population were found in the age groups 65-69 years (147.6±2.7), 70-74 years (159.3±2.5), and 75-79 years (147.1±3.2). The incidence of LC tended to increase only at the age of 80-84 years (APC=+1.26) and the most pronounced average annual decline rates were observed in the age groups of 45-49 years (APC=−4.09), 50-54 years (APC=−4.20) and 85+ years (APC=−4.07). The average annual standardized incidence rate was 22.2 per 100,000, and in dynamics tended to decrease (APC=−2.04). There is a decrease in incidence in almost all regions, with the exception of the Mangystau region (APC=+1.65). During the compilation of cartograms, incidence rates were determined on the basis of standardized indicators: low – up to 20.6, average – from 20.6 to 25.6, high – above 25.6 per 100,000 for the entire population. Conclusion: The incidence of lung cancer in Kazakhstan is decreasing. The incidence among the male population is six times higher than among the female, while the rate of decline is more pronounced. The incidence tends to decrease in almost all regions. High rates were found in the northern and eastern regions.
Collagen-Laponite Nanoclay Hydrogels for Tumor Spheroid Growth

The extracellular matrix (ECM) plays an important regulatory role in the development and progression of tumoral tissue. Its functions and properties are crucial in determining tumor cell behavior such as invasion, migration, and malignancy development. Our study explores the role of collagen type I in cancer development and spread using engineered tumor models like multicellular spheroids grown in collagen-based hydrogels to simulate early tumor formation. We employ microfluidic techniques to test the hypothesis that (i) adding Laponite nanoclay to collagen hydrogels modifies mechanical and rheological properties and (ii) changing the stiffness of the collagen microenvironment affects tumor spheroid growth. Our findings support our theories and suggest the use of ECM components and engineered tumor models in cancer research, offering a biocompatible and biomimetic method to tailor the mechanical properties of conventional collagen hydrogels.
Transesophageal echocardiography‐guided versus fluoroscopy‐guided patent foramen ovale closure: A single center registry

Percutaneous closure of patent foramen ovale (PFO) is conventionally performed under continuous transesophageal echocardiographic (TEE) guidance. We aimed to evaluate whether a simplified procedural approach, including pure fluoroscopy‐guidance and final TEE control, as well as an aimed ‘next‐day‐discharge’ is comparable with the conventional TEE‐guided procedure in terms of periprocedural and intermediate‐term outcomes.
REGRESSION FOR ANALYSIS OF GENOMIC DATA

We consider estimation and variable selection in high-dimensional Cox regression when a prior knowledge of the relationships among the covariates, de- scribed by a network or graph, is available. A limitation of the existing methodology for survival analysis with high-dimensional genomic data is that a wealth of struc- tural information about many biological processes, such as regulatory networks and pathways, has often been ignored. In order to incorporate such prior network information into the analysis of genomic data, we propose a network-based regu- larization method for high-dimensional Cox regression, by using an '1-penalty to induce sparsity of the regression coecients and a quadratic Laplacian penalty to encourage smoothness between the coecients of neighboring variables on a given network. The proposed method is implemented by an ecient coordinate descent algorithm. In the setting where the dimensionality p may grow exponentially fast with the sample size n, we establish model selection consistency and estimation bounds for the proposed estimators. The theoretical results provide insights into the gain from taking into account the network structural information. Extensive simulation studies indicate that our method outperforms Lasso and elastic net in terms of variable selection accuracy and stability. We apply our method to a breast cancer gene expression study and identify several biologically plausible subnetworks and pathways that are associated with breast cancer distant metastasis.
Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals

ABSTRACT Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusions: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.
Mutations in AcrR and RNA Polymerase Confer High-Level Resistance to Psoralen-UVA Irradiation

Psoralen DNA interstrand cross-links are highly toxic lesions with antimicrobial and anticancer properties. Despite the lack of effective mechanisms for repair, cells can become resistant to cross-linking agents through mechanisms that remain poorly defined. ABSTRACT DNA interstrand cross-links, such as those formed by psoralen-UVA irradiation, are highly toxic lesions in both humans and bacteria, with a single lesion being lethal in Escherichia coli. Despite the lack of effective repair, human cancers and bacteria can develop resistance to cross-linking treatments, although the mechanisms of resistance remain poorly defined. Here, we subjected E. coli to repeated psoralen-UVA exposure to isolate three independently derived strains that were >10,000-fold more resistant to this treatment than the parental strain. Analysis of these strains identified gain-of-function mutations in the transcriptional regulator AcrR and the alpha subunit of RNA polymerase that together could account for the resistance of these strains. Resistance conferred by the AcrR mutation is mediated at least in part through the regulation of the AcrAB-TolC efflux pump. Resistance via mutations in the alpha subunit of RNA polymerase occurs through a still-uncharacterized mechanism that has an additive effect with mutations in AcrR. Both acrR and rpoA mutations reduced cross-link formation in vivo. We discuss potential mechanisms in relation to the ability to repair and survive interstrand DNA cross-links. IMPORTANCE Psoralen DNA interstrand cross-links are highly toxic lesions with antimicrobial and anticancer properties. Despite the lack of effective mechanisms for repair, cells can become resistant to cross-linking agents through mechanisms that remain poorly defined. We derived resistant mutants and identified that two gain-of-function mutations in AcrR and the alpha subunit of RNA polymerase confer high levels of resistance to E. coli treated with psoralen-UVA. Resistance conferred by AcrR mutations occurs through regulation of the AcrAB-TolC efflux pump, has an additive effect with RNA polymerase mutations, acts by reducing the formation of cross-links in vivo, and reveals a novel mechanism by which these environmentally and clinically important agents are processed by the cell.
Polymorphisms in TIE2 and ANGPT-1 genes are associated with protection against diabetic retinopathy in a Brazilian population

ABSTRACT Objective: The objective of this study was to investigate the association between SNPs in the TIE2 and ANGPT-1 genes and diabetic retinopathy (DR). Subjects and methods: This study comprised 603 patients with type 2 diabetes mellitus (T2DM) and DR (cases) and 388 patients with T2DM for more than 10 years and without DR (controls). The TIE2 rs639225 (A/G) and rs638203 (A/G) SNPs and the ANGPT-1 rs4324901 (G/T) and rs2507800 (T/A) SNPs were genotyped by real-time PCR using TaqMan MGB probes. Results: The G/G genotype of the rs639225/TIE2, the G/G genotype of the rs638203/TIE2 and the T allele of the rs4324901/ANGPT-1 SNPs were associated with protection against DR after adjustment for age, glycated hemoglobin, gender, and presence of hypertension (P = 0.042, P = 0.003, and P = 0.028, respectively). No association was found between the rs2507800/ANGPT-1 SNP and DR. Conclusion: We demonstrated, for the first time, the association of TIE2 rs638203 and rsrs939225 SNPs and ANGPT-1 rs4324901 SNP with protection against DR in a Brazilian population.
Psychometric Properties of the MMPI-3 in a Sample of Black and White American Undergraduate Students: Examining Group Differences and Convergent/Discriminant Validity with the ASEBA Adult Self-Report

Abstract The current study examined MMPI-3 internal and external psychometric properties with a focus on the impact of racialized group membership (Black and White Americans). The second aim was to examine convergent/discriminant MMPI-3 scale associations with a different broadband, hierarchical self-report assessment tool [Adult Self-Report (ASR)]. Consistent with findings on prior MMPI iterations, we expected to observe no clinically meaningful mean differences on MMPI-3 scale T-scores. We hypothesized that validity coefficients between MMPI-3 and ASR scales measuring similar constructs would be stronger (convergent validity) and the inverse for scales measuring disparate constructs (discriminant validity). We also expected coefficient magnitude consistency across racial groups. The final sample was composed of 254 undergraduates (74.4% female; 63.8% White, 36.2% Black). Results suggest 1) MMPI-3 substantive scale mean T-scores are comparable between White and Black American undergraduates; 2) MMPI-3 scales correlate with ASR scale scores in expected ways with regard to internalizing problems, rule breaking and impulsivity, thought problems, and substance use (but not overall externalizing, aggression, attention problems, and intrusiveness); and 3) convergent and discriminant associations between MMPI-3 and ASR scales are consistent across White and Black Americans. This work provides support for MMPI-3 use with racially diverse individuals, considers next steps for understanding MMPI-3 scale score functioning in diverse populations, and provides novel information on MMPI-3 correspondence with the ASR.