Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth.

BACKGROUND Interleukin-8 (IL-8) is a proangiogenic cytokine that is overexpressed in many human cancers. We investigated the clinical and biologic significance of IL-8 in ovarian carcinoma using human samples and orthotopic mouse models. METHODS Tumor expression of IL-8 was assessed by immunohistochemistry among ovarian cancer patients (n = 102) with available clinical and survival data. We examined the effect of IL-8 gene silencing with small interfering RNAs incorporated into neutral liposomes (siRNA-DOPCs), alone and in combination with docetaxel, on in vivo tumor growth, angiogenesis (microvessel density), and tumor cell proliferation in mice (n = 10 per treatment group) bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) and taxane-resistant (SKOV3ip2.TR) ovarian tumors. All statistical tests were two-sided. RESULTS Of the 102 cancer specimens, 43 (42%) had high IL-8 expression and 59 (58%) had low or no IL-8 expression; high IL-8 expression was associated with advanced tumor stage (P = .019), high tumor grade (P = .031), and worse survival (median survival for patients with high vs low IL-8 expression: 1.62 vs 3.79 years; P < .001). Compared with empty liposomes, IL-8 siRNA-DOPC reduced the mean tumor weight by 32% (95% confidence interval [CI] = 14% to 50%; P = .03) and 52% (95% CI = 27% to 78%; P = .03) in the HeyA8 and SKOV3ip1 mouse models, respectively. In all three mouse models, treatment with IL-8 siRNA-DOPC plus the taxane docetaxel reduced tumor growth the most compared with empty liposomes (77% to 98% reduction in tumor growth; P < .01 for all). In the HeyA8 and SKOV3ip1 models, tumors from mice treated with IL-8 siRNA-DOPC alone had lower microvessel density than tumors from mice treated with empty liposomes (HeyA8: 34% lower, 95% CI = 32% to 36% lower [P = .002]; SKOV3ip1: 39% lower, 95% CI = 34% to 44% lower [P = .007]). Compared with empty liposomes, IL-8 siRNA-DOPC plus docetaxel reduced tumor cell proliferation by 35% (95% CI = 25% to 44%; P < .001) and 38% (95% CI = 28% to 48%; P < .001) in the HeyA8 and SKOV3ip1 models, respectively. CONCLUSIONS Increased IL-8 expression is associated with poor clinical outcome in human ovarian carcinoma, and IL-8 gene silencing decreases tumor growth through antiangiogenic mechanisms.
Evaluation of the USE IT-questionnaire for the Evaluation of the Adoption of Electronic Patient Records by Healthcare Professionals

Summary Background: A combined quantitative and qualitative socio-technical approach is applied in two evaluation studies of electronic patient records (EPR). In these studies the focus was on factors influencing the adoption of the EPR by care providers. Objective: The research approach is based on the USE IT-model. In addition to the USE IT-interview model, the USE IT-questionnaire is presented and evaluated in order to pre sent a valid and useful integrated approach for the evaluation of IT-adoption in healthcare. Methods: The USE IT-questionnaire was evaluated by applying a principal component analysis of the quantitative results in two cases (n = 222), and by comparison of the resulting factors with the determinants of the USE IT-model. Results: The factor analysis of the USE IT-questionnaire resulted in six valid factors: 1. Task support satisfaction, 2. Interface satisfaction, 3. Compatibility, 4. Collaboration, 5. Learnability, and 6. Accessibility. The questions about resources did not combine into a factor. Conclusion: The detailed questions of the questionnaire lead to decomposition of the constructs Task support satisfaction and Ease of use into factors. The construct Task support satisfaction which was supposed to measure relevance was decomposed in two factors measuring relevance and two factors measuring micro-requirements.
Directed Evolution of Toluene ortho-Monooxygenase for Enhanced 1-Naphthol Synthesis and Chlorinated Ethene Degradation

ABSTRACT Trichloroethylene (TCE) is the most frequently detected groundwater contaminant, and 1-naphthol is an important chemical manufacturing intermediate. Directed evolution was used to increase the activity of toluene ortho-monooxygenase (TOM) of Burkholderia cepacia G4 for both chlorinated ethenes and naphthalene oxidation. When expressed in Escherichia coli, the variant TOM-Green degraded TCE (2.5 ± 0.3 versus 1.39 ± 0.05 nmol/min/mg of protein), 1,1-dichloroethylene, and trans-dichloroethylene more rapidly. Whole cells expressing TOM-Green synthesized 1-naphthol at a rate that was six times faster than that mediated by the wild-type enzyme at a concentration of 0.1 mM (0.19 ± 0.03 versus 0.029 ± 0.004 nmol/min/mg of protein), whereas at 5 mM, the mutant enzyme was active (0.07 ± 0.03 nmol/min/mg of protein) in contrast to the wild-type enzyme, which had no detectable activity. The regiospecificity of TOM-Green was unchanged, with greater than 97% 1-naphthol formed. The beneficial mutation of TOM-Green is the substitution of valine to alanine in position 106 of the α-subunit of the hydroxylase, which appears to act as a smaller “gate” to the diiron active center. This hypothesis was supported by the ability of E. coli expressing TOM-Green to oxidize the three-ring compounds, phenanthrene, fluorene, and anthracene faster than the wild-type enzyme. These results show clearly that random, in vitro protein engineering can be used to improve a large multisubunit protein for multiple functions, including environmental restoration and green chemistry.
Reverse-Phase Protein Array Profiling of Oropharyngeal Cancer and Significance of PIK3CA Mutations in HPV-Associated Head and Neck Cancer

Purpose: Human papilloma virus (HPV)–associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) have different molecular and biologic characteristics and clinical behavior compared with HPV-negative (HPV−) OPSCC. PIK3CA mutations are more common in HPV(+) OPSCC. To define molecular differences and tumor subsets, protein expression and phosphorylation were compared between HPV(+) and HPV(−) OPSCC and between tumors with and without PIK3CA mutations. Experimental Design: Expression of 137 total and phosphorylated proteins was evaluated by reverse-phase protein array in 29 HPV(+) and 13 HPV(−) prospectively collected OPSCCs. Forty-seven OPSCCs were tested for hotspot-activating mutations in PIK3CA and AKT. Activation of PIK3CA downstream targets and sensitivity to pathway inhibitors were determined in HPV(+) head and neck cancer cells overexpressing wild-type or mutant PIK3CA. Results: Analyses revealed 41 differentially expressed proteins between HPV(+) and HPV(−) OPSCC categorized into functional groups: DNA repair, cell cycle, apoptosis, phosphoinositide 3-kinase (PI3K)/AKT/mTOR, and receptor kinase pathways. All queried DNA repair proteins were significantly upregulated in HPV(+) samples. A total of 8 of 33 HPV(+) and 0 of 14 HPV(−) tumors contained activating PIK3CA mutations. Despite all activating PIK3CA mutations occurring in HPV(+) samples, HPV(+) tumors had lower mean levels of activated AKT and downstream AKT target phosphorylation. Ectopic expression of mutant PIK3CA in HPV(+) cells increased mTOR, but not AKT activity. HPV E6/E7 overexpression inhibited AKT phosphorylation in HPV-negative cells. Mutant PIK3CA overexpressing cells were more sensitive to a dual PI3K/mTOR inhibitor compared with an AKT inhibitor. Conclusions: Protein expression analyses suggest that HPV(+) and HPV(−) OPSCC differentially activate DNA repair, cell cycle, apoptosis, PI3K/AKT/mTOR, and receptor kinase pathways. PIK3CA mutations are more common in HPV(+) OPSCC and are associated with activation of mTOR, but not AKT. These data suggest that inhibitors for mTOR may have activity against HPV(+) PIK3CA mutant oropharyngeal cancers. Clin Cancer Res; 20(9); 2300–11. ©2014 AACR.
Subsurface Fine-Scale Patterns in an Anticyclonic Eddy Off Cap-Vert Peninsula Observed From Glider Measurements

Glider measurements acquired along four transects between Cap-Vert Peninsula and theCape Verde archipelago in the eastern tropical North Atlantic during March–April 2014 were used to investigate fine-scale stirring in an anticyclonic eddy. The anticyclone was formed near 12°N off the continental shelf and propagated northwest toward the Cape Verde islands. At depth, between 100 and–400 m, the isolated anticyclone core contained relatively oxygenated, low-salinity South Atlantic CentralWater, while the surrounding water masses were saltier and poorly oxygenated. The dynamical and thermohaline subsurface environment favored the generation offine-scale horizontal and vertical temperature and salinity structures in and around the core of the anticyclone. These features exhibited horizontal scales of O(10–30 km) relatively small with respect to the eddy radius of O(150 km). The vertical scales of O(5–100 m) were associated to density-compensated gradient. Spectra of salinity and oxygen along isopycnals revealed a slope of around k-2in the 10- to 100-km horizontal scale range.Further analyses suggest that the fine-scale structures are likely related to tracer stirring processes. Such mesoscale anticyclonic eddies and the embedded fine-scale tracers in and around them could play a major role in the transport of South Atlantic Central Water masses and ventilation of the North Atlantic Oxygen Minimum Zone.
Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals

Purpose: To develop educational guidelines for the diagnostic confirmation and management of individuals identified by newborn screening, family-based testing after proband identification, or carrier testing in at-risk populations, and subsequent prenatal or postnatal testing of those who are presymptomatic for a lysosomal storage disease.Methods: Review of English language literature and discussions in a consensus development panel comprised an international group of experts in the clinical and laboratory diagnosis, treatment and management, newborn screening, and genetic aspects of lysosomal storage diseases.Results: Although clinical trial and longitudinal data were used when available, the evidence in the literature is limited and consequently the recommendations must be considered as expert opinion. Guidelines were developed for Fabry, Gaucher, and Niemann-Pick A/B diseases, glycogen storage type II (Pompe disease), globoid cell leukodystrophy (Krabbe disease), metachromatic leukodystrophy, and mucopolysaccharidoses types I, II, and VI.Conclusion: These guidelines serve as an educational resource for confirmatory testing and subsequent clinical management of presymptomatic indivduals suspected to have a lysosomal storage disease; they also help to define a research agenda for longitudinal studies such as the American College of Medical Genetics/National Institutes of Health Newborn Screening Translational Research Network.
The Prevalence of Depression among Patients with the Top Ten Most Common Cancers in South Korea

Objective Among the various psychiatric disorders, depression is a common comorbid condition in cancer patients. Due to the distinct and diverse nature of cancer, the prevalence of depression may be assumed to be affected by differences in primary cancer sites. In this study, we explored the prevalence rates of depression among the ten most prevalent cancers in South Korea using a national patient sample. Methods This was a 1-year cross-sectional study using a national patient sample provided by the South Korean National Health Insurance in 2011. We selected all patients who had received ICD-10 codes of the 10 most prevalent cancers and major depressive disorder. Afterwards, the cancer and depression groups were merged and analyzed. Results The MDD prevalence rate was highest in lung cancer (11.0%), followed by non-Hodgkin's lymphoma (9.2%), prostate (9.1%), bladder (8.8%), breast (7.8%), cervix (7.8%), colorectal (7.7%), stomach (6.9%), liver (6.5%), and thyroid cancer (5.6%). Within all cancer groups, patients with a MDD diagnosis were significantly older (p<0.05) than non-MDD patients. Colorectal, stomach, and thyroid cancer displayed a higher female proportion in the MDD group than the non-MDD group. In the subgroup analysis, the prevalence rate differed by age and sex. Conclusion The prevalence of depression varied according to cancer types. Patients with lung cancer were the most prone to experience depression. Because clinical and psychological factors may influence MDD prevalence, these factors will need to be studied more closely in the future.
Clonal Expansion and Emergence of Environmental Multiple-Triazole-Resistant Aspergillus fumigatus Strains Carrying the TR34/L98H Mutations in the cyp51A Gene in India

Azole resistance is an emerging problem in Aspergillus which impacts the management of aspergillosis. Here in we report the emergence and clonal spread of resistance to triazoles in environmental Aspergillus fumigatus isolates in India. A total of 44 (7%) A. fumigatus isolates from 24 environmental samples were found to be triazole resistant. The isolation rate of resistant A. fumigatus was highest (33%) from soil of tea gardens followed by soil from flower pots of the hospital garden (20%), soil beneath cotton trees (20%), rice paddy fields (12.3%), air samples of hospital wards (7.6%) and from soil admixed with bird droppings (3.8%). These strains showed cross-resistance to voriconazole, posaconazole, itraconazole and to six triazole fungicides used extensively in agriculture. Our analyses identified that all triazole-resistant strains from India shared the same TR34/L98H mutation in the cyp51 gene. In contrast to the genetic uniformity of azole-resistant strains the azole-susceptible isolates from patients and environments in India were genetically very diverse. All nine loci were highly polymorphic in populations of azole-susceptible isolates from both clinical and environmental samples. Furthermore, all Indian environmental and clinical azole resistant isolates shared the same multilocus microsatellite genotype not found in any other analyzed samples, either from within India or from the Netherlands, France, Germany or China. Our population genetic analyses suggest that the Indian azole-resistant A. fumigatus genotype was likely an extremely adaptive recombinant progeny derived from a cross between an azole-resistant strain migrated from outside of India and a native azole-susceptible strain from within India, followed by mutation and then rapid dispersal through many parts of India. Our results are consistent with the hypothesis that exposure of A. fumigatus to azole fungicides in the environment causes cross-resistance to medical triazoles. The study emphasises the need of continued surveillance of resistance in environmental and clinical A. fumigatus strains.
DAP kinase-a proapoptotic gene that functions as a tumor suppressor.

Having a major impact on tumor initiation, progression, and metastasis, apoptosis has become a subject that draws tremendous attention and research efforts in the cancer field. At various stages during tumor development, cells are subjected to stressful conditions that trigger programmed cell death, and thus mutations leading to inhibition of apoptosis confer a selective advantage to cells. In premalignant cells, activation of oncogenes and the consequent hyperproliferation provoke a cellular response that leads to elimination of those cells by apoptosis. Subsequently, transformed cells in the tumor microenvironment are under constant selective pressure, such as lack of oxygen (hypoxia), depletion of growth/survival factors, attacks by the immune system, and often death by anoikis due to loss of cell–matrix interactions. At later stages, when metastasizing tumor cells enter into circulation they encounter many additional death-inducing signals such as superoxides, nitric oxides, killing cytokines, and mechanical shearing forces. Thus, all along the multistage process of tumorigenesis induction of apoptosis functions as a tumor-suppressor mechanism and cells have to escape from various inducers of apoptosis in order to survive (reviewed in Kaufmann and Gores, 2000; Lowe and Lin, 2000; Wyllie et al., 1999). This means that tumor cells should benefit from mutations that either inactivate various intracellular proteins which positively mediate programmed cell death or activate antiapoptotic genes. The first example which established the concept that genes in the apoptotic machinery are mutated in cancer was documented with the cloning of Bcl-2. The initial findings that this gene resides at the site of (8;14) chromosomal translocation characteristic of follicular B cell lymphoma (Tsujimoto et al., 1984) were followed by the elegant studies performed in transgenic mice models which altogether established a role for Bcl-2 activation in promoting cell survival and in vivo lymphomagenesis (McDonnell et al., 1989;
Inhibition of Influenza A Virus Infection In Vitro by Peptides Designed In Silico

Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, capable of causing severe human respiratory infections. Currently, only two types of drugs are used to treat influenza A infections, the M2 H+ ion channel blockers (amantadine and rimantadine) and the neuraminidase inhibitors (NAI) (oseltamivir and zanamivir). Moreover, the emergence of drug-resistant influenza A virus strains has emphasized the need to develop new antiviral agents to complement or replace the existing drugs. Influenza A virus has on the surface a glycoprotein named hemagglutinin (HA) which due to its important role in the initial stage of infection: receptor binding and fusion activities of viral and endosomal membranes, is a potential target for new antiviral drugs. In this work we designed nine peptides using several bioinformatics tools. These peptides were derived from the HA1 and HA2 subunits of influenza A HA with the aim to inhibit influenza A virus infection. The peptides were synthetized and their antiviral activity was tested in vitro against several influenza A viral strains: Puerto Rico/916/34 (H1N1), (H1N1)pdm09, swine (H1N1) and avian (H5N2). We found these peptides were able to inhibit the influenza A viral strains tested, without showing any cytotoxic effect. By docking studies we found evidence that all the peptides were capable to bind to the viral HA, principally to important regions on the viral HA stalk, thus could prevent the HA conformational changes required to carry out its membranes fusion activity.
Turbo Equalization: An Overview

Turbo codes and the iterative algorithm for decoding them sparked a new era in the theory and practice of error control codes. Turbo equalization followed as a natural extension to this development, as an iterative technique for detection and decoding of data that has been both protected with forward error correction and transmitted over a channel with intersymbol interference (ISI). In this paper, we review the turbo equalization approach to coded data transmission over ISI channels, with an emphasis on the basic ideas, some of the practical details, and many of the research directions that have arisen from this offshoot, introduced by Douillard, of the original turbo decoding algorithm. The subsequent relaxation of the maximum a posteriori (MAP) equalization algorithm to include linear and other simpler receivers sparked a decade and a half of research into iterative algorithms, spanning research problems ranging from trellis coded modulation to underwater acoustic communications.
Acute Changes in Lung Histopathology and Bronchoalveolar Lavage Parameters in Mice Exposed to the Choking Agent Gas Phosgene

Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonary edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveolar lavage fl uid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m 3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to fi ltered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes. At 1, 4, 8, 12, 24, 48, and 72 hours after exposure each group of mice was euthanized and processed for histopathology, bronchoalveolar lavage or gravimetric measurements, respectively. Over time, the histopathological lesions were characterized by acute changes consisting of alveolar and interstitial edema, fi brin and hemorrhage, followed by signifi cant alveolar and interstitial fl ooding with infl ammatory cell infi ltrates and scattered bronchiolar and terminal airway epithelial degeneration and necrosis. From 48 to 72 hours, there was partial resolution of the edema and degenerative changes, followed by epithelial and fi broblastic regeneration centered on the terminal bronchiolar areas. Bronchoalveolar lavage was processed for cell differential counts, LDH, and protein determination. Comparative analysis revealed signifi cant increases in both postexposure lung wet/dry weight ratios, and early elevations of BALF LDH and protein, and later elevations in leukocytes. This article describes the use of histopathology to chronicle the temporal pulmonary changes subsequent to whole body exposure to phosgene, and correlate these changes with BALF ingredients and postexposure lung wet weights in an effort to characterize toxic gas-induced acute lung injury and identify early markers of phosgene exposure.
Effect of Environmental and Socioeconomic Factors on Increased Early Childhood Blood Lead Levels: A Case Study in Chicago

This study analyzes the prevalence of elevated blood lead levels (BLLs) in children across Chicagoland zip codes from 2019 to 2021, linking them to socioeconomic, environmental, and racial factors. Wilcoxon tests and generalized additive model (GAM) regressions identified economic hardship, reflected in per capita income and unemployment rates, as a significant contributor to increased lead poisoning (LP) rates. Additionally, LP rates correlate with the average age of buildings, particularly post the 1978 lead paint ban, illustrating policy impacts on health outcomes. The study further explores the novel area of land surface temperature (LST) effects on LP, finding that higher nighttime LST, indicative of urban heat island effects, correlates with increased LP. This finding gains additional significance in the context of anthropogenic climate change. When these factors are combined with the ongoing expansion of urban territories, a significant risk exists of escalating LP rates on a global scale. Racial disparity analysis revealed that Black and Hispanic/Latino populations face higher LP rates, primarily due to unemployment and older housing. The study underscores the necessity for targeted public health strategies to address these disparities, emphasizing the need for interventions that cater to the unique challenges of these at-risk communities.