Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Epidermal Growth Factor Receptor Mutations in Patients with Non-Small Cell Lung Cancer in Turkish Population

Aims: Epidermal growth factor receptor mutation analysis in non-small cell lung cancer is important for selecting patients who will receive treatment with tyrosine kinase inhibitors. In this study, we aimed to investigate the prevalence of epidermal growth factor receptor mutations and mutation patterns in the Turkish population. Methods: We retrospectively reviewed molecular pathology reports of 959 cases with lung cancer analysed for epidermal growth factor receptor mutations. We analysed all four epidermal growth factor receptor exon mutations using a real-time polymerase chain reaction platform. Results: In this study, the epidermal growth factor receptor mutation rate in the Turkish population was 16.7% (160 of 959). The epidermal growth factor receptor mutation frequency was significantly higher in women (37.1%, n=96) than in men (9.1%, n=64) (p<0.001). In addition, the epidermal growth factor receptor mutation rate was higher in the adenocarcinoma histologic type (p<0.001). Patients with mutations were older than those without mutations (p=0.003). The most frequent mutations were exon 19 deletions (48.8%, 78/160) and exon 21 L858R point mutations (38.1.1%, 61/160). We also detected compound mutation patterns in three cases (1.9%). Conclusion: The prevalence of epidermal growth factor receptor mutations in the Turkish population was slightly higher than that in the Caucasian population and lower than that in the East Asian population. The results of this study may provide guidance in personalized therapy of non-small cell lung cancer in the Turkish population.
Study of the AES-like Super Boxes in LED and PHOTON

In this paper we investigate the choice of S-box and MDS-matrix in AES-like super box structures. Before giving the theory, we first study the super boxes of the led block cipher and the photon hash function and compute the distribution of all two-round characteristics when there is a key addition in the round function. Then, we compare these results with a fixed key (i.e. using the given constant values) in the round function. We observe that the results are consistent with the theory (following the approach of plateau characteristics) except for some extreme cases. Next, we discuss the effect of the S-box size for a fixed size super box. We show that the number of right pairs increases if the size of S-box decreases. Moreover, we study the effect of MDS-matrix with the previous setting by using a circulant matrix and the special MDS-matrix used in the design of led.
The Good, the Bad and the Recovery in an Assisted Migration

Background Assisted migration or translocation of species to ameliorate effects of habitat loss or changing environment is currently under scrutiny as a conservation tool. A large scale experiment of assisted migration over hundreds of kilometres was tested on a morph from a commercial fishery of southern rock lobster Jasus edwardsii, to enhance depleted populations, improve the yield and sustainability of the fishery, and test resilience to a changing climate. Methodology and Principal Findings Approximately 10,000 lower-valued, pale-coloured lobsters were moved from deep water to inshore sites (2 in Tasmania [TAS] and 2 in South Australia [SA]) where the high-value, red morph occurs. In TAS this was a northwards movement of 1° latitude. Growth was measured only in TAS lobsters, and reproductive status was recorded in lobsters from all locations. Pale females (TAS) grew 4 times faster than resident pale lobsters from the original site and twice as fast as red lobsters at their new location. Approximately 30% of translocated pale lobsters deferred reproduction for one year after release (SA and TAS), and grew around 1 mm yr−1 less compared to translocated pale lobsters that did not defer reproduction. In spite of this stress response to translocation, females that deferred reproduction still grew 2–6 mm yr−1 more than lobsters at the source site. Lobsters have isometric growth whereby volume increases as a cube of length. Consequently despite the one-year hiatus in reproduction, increased growth increases fecundity of translocated lobsters, as the increase in size provided a larger volume for producing and incubating eggs in future years. Conclusions and Significance Assisted migration improved egg production and growth, despite a temporary stress response, and offers a tool to improve the production, sustainability and resilience of the fishery.
Educational inequality in Rio de Janeiro and its impact on multimorbidity: evidence from the Pró-Saúde study. A cross-sectional analysis

ABSTRACT BACKGROUND: Information about multimorbidity is scarce in developing countries. This study aimed to estimate the association of educational attainment with occurrences of multimorbidity in a population of public employees on university campuses in Rio de Janeiro. DESIGN AND SETTING: We conducted cross-sectional analyses on baseline data (1999-2001) from 3,253 participants in the Pró-Saúde study, conducted in Brazil. METHODS: The prevalence of multimorbidity, defined as a self-reported history of medical diagnoses of two or more chronic conditions, was estimated according to sex, age, smoking, obesity and educational level. The association between education and multimorbidity was estimated using odds ratios (OR) and the relative and slope indices of inequality, in order to quantify the degree of educational inequality among individuals with multimorbidity in this population. RESULTS: Greater age, female sex, smoking and obesity had direct associations with multimorbidity; and tobacco exposure and obesity also showed direct relationships with poorer educational level. There was a monotonic inverse linear trend between educational level and the presence of multimorbidity among women, with twice the odds (OR 2.47; 95% confidence interval, CI: 1.42-4.40) between extremities of schooling categories. There was excess multimorbidity of 22% at the lowest extremity of schooling, thus showing that women with worse educational status were more affected by the outcome. No trend and no excess multimorbidity was seen among men. CONCLUSIONS: Educational inequality is an important determinant for development of multimorbidity. Men and women experience its effect differently. Researchers need to consider that sex may be an effect modifier in multimorbidity studies.
Dynamic practical stabilization of sampled-data linear distributed parameter systems

In this paper, dynamic practical stability properties of infinite-dimensional sampled-data systems are discussed. A family of finite-dimensional discrete-time controllers are first designed to uniformly exponentially stabilize numerical approximate models that are obtained from space and time discretization. Sufficient conditions are provided to ensure that these controllers can be used to drive trajectories of infinite-dimensional sampled-data systems to a neighborhood of the origin by properly tuning the sampling period, space and time discretization parameters and choosing an appropriate filtering process for initial conditions.
Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for limb-girdle muscular dystrophy 2D

Abstract Limb-girdle muscular dystrophy type 2D (LGMD2D) is a rare autosomal-recessive disease, affecting striated muscle, due to mutation of SGCA, the gene coding for α-sarcoglycan. Nowadays, more than 50 different SGCA missense mutations have been reported. They are supposed to impact folding and trafficking of α-sarcoglycan because the defective polypeptide, although potentially functional, is recognized and disposed of by the quality control of the cell. The secondary reduction of α-sarcoglycan partners, β-, γ- and δ-sarcoglycan, disrupts a key membrane complex that, associated to dystrophin, contributes to assure sarcolemma stability during muscle contraction. The complex deficiency is responsible for muscle wasting and the development of a severe form of dystrophy. Here, we show that the application of small molecules developed to rescue ΔF508-CFTR trafficking, and known as CFTR correctors, also improved the maturation of several α-sarcoglycan mutants that were consequently rescued at the plasma membrane. Remarkably, in myotubes from a patient with LGMD2D, treatment with CFTR correctors induced the proper re-localization of the whole sarcoglycan complex, with a consequent reduction of sarcolemma fragility. Although the mechanism of action of CFTR correctors on defective α-sarcoglycan needs further investigation, this is the first report showing a quantitative and functional recovery of the sarcoglycan-complex in human pathologic samples, upon small molecule treatment. It represents the proof of principle of a pharmacological strategy that acts on the sarcoglycan maturation process and we believe it has a great potential to develop as a cure for most of the patients with LGMD2D.
Transcatheter versus surgical aortic valve replacement in moderate and high-risk patients: a meta-analysis

Objectives The evidence of the benefits of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for patients of high or intermediate surgical risk is not consistent. We performed a meta-analysis to compare major adverse outcomes after TAVR or SAVR. Methods We searched propensity score matched studies or randomized clinical trials comparing the risks of mortality, stroke, major bleeding, acute renal injury, pacemaker implantation, vascular complications and prostheses haemodynamic performance between TAVR and SAVR in patients with moderate or high risk. Combined odds ratios (ORs), relative risk or mean differences with corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Analyses of sensitivity and publication bias were also conducted. Results We included 5 clinical trials and 37 observational studies, enrolling 20 224 patients (TAVR, n = 9099 and SAVR, n = 11 125). The pooled analysis suggested no differences in early (OR = 1.11, 95% CI 0.9-1.39, P = 0.355) or late mortality (relative risk = 0.91, 95% CI 0.78-1.05, P = 0.194). TAVR was associated with a lower risk of major bleeding (OR = 0.42, 95% CI 0.25-0.69, P < 0.001) and acute kidney injury (OR = 0.51, 95% CI 0.34-0.71) but with an increase in the incidence of pacemaker implantation (OR = 2.31, 95% CI 1.73-3.08) and vascular complications (OR = 4.88, 95% CI 2.84-8.39). Residual aortic regurgitation was more frequent after TAVR (OR= 6.83, 95% CI 4.87-9.6). SAVR prostheses were associated with poor trans-prosthetic gradients (mean difference: -2.4 mmHg, 95% CI - 3.27 to - 1.53). Conclusions TAVR and SAVR have similar short and long-term all-cause mortality and risk of stroke among patients of moderate or high surgical risk. TAVR decreases the risk of major bleeding, acute kidney injury and improves haemodynamic performance compared with SAVR but increases the risk of vascular complications, the need for a pacemaker and residual aortic regurgitation.
Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC)

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case–control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04–1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI–multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1–1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25–<30 kg/m2) or obese (30+ kg/m2) in both younger and usual adulthood (vs. individuals consistently <25 kg/m2), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876–85. ©2017 AACR.
Point process models for localization and interdependence of punctate cellular structures

Accurate representations of cellular organization for multiple eukaryotic cell types are required for creating predictive models of dynamic cellular function. To this end, we have previously developed the CellOrganizer platform, an open source system for generative modeling of cellular components from microscopy images. CellOrganizer models capture the inherent heterogeneity in the spatial distribution, size, and quantity of different components among a cell population. Furthermore, CellOrganizer can generate quantitatively realistic synthetic images that reflect the underlying cell population. A current focus of the project is to model the complex, interdependent nature of organelle localization. We built upon previous work on developing multiple non‐parametric models of organelles or structures that show punctate patterns. The previous models described the relationships between the subcellular localization of puncta and the positions of cell and nuclear membranes and microtubules. We extend these models to consider the relationship to the endoplasmic reticulum (ER), and to consider the relationship between the positions of different puncta of the same type. Our results do not suggest that the punctate patterns we examined are dependent on ER position or inter‐ and intra‐class proximity. With these results, we built classifiers to update previous assignments of proteins to one of 11 patterns in three distinct cell lines. Our generative models demonstrate the ability to construct statistically accurate representations of puncta localization from simple cellular markers in distinct cell types, capturing the complex phenomena of cellular structure interaction with little human input. This protocol represents a novel approach to vesicular protein annotation, a field that is often neglected in high‐throughput microscopy. These results suggest that spatial point process models provide useful insight with respect to the spatial dependence between cellular structures. © 2016 International Society for Advancement of Cytometry
Genotype-specific methylation of HPV in cervical intraepithelial neoplasia

Objective Hypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings. Methods Cervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR). Results The degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2. Conclusion Our study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
Analysis of Design Parameters Reducing the Damage Rate of Low-Noise Amplifiers Affected by High-Power Electromagnetic Pulses

To protect the RF front end from electronic warfare, many studies have focused on damage phenomena of the low-noise amplifiers (LNAs). Existing studies have focused on the damage points of semiconductor devices because the peripheral circuit elements of LNAs are less susceptible to breakdown than nonlinear elements. However, their theoretical analysis is insufficient to explain the damage mechanism of LNAs under conditions such as changes in input power, frequency, and design parameters. To analyze the relationship between damage rate and parameters of the peripheral circuit of an LNA, this paper proposes a new definition of the power absorbed to a nonlinear element when input power to an LNA is very high by high-power electromagnetic pulses. In addition, LNAs having different input impedances and output impedances are designed to verify the power absorption. From the results, this paper identified parameters that increase the damage rate of LNAs, and suggested designs to reduce the damage rate.
Microbial and Chemical Characterization of Underwater Fresh Water Springs in the Dead Sea

Due to its extreme salinity and high Mg concentration the Dead Sea is characterized by a very low density of cells most of which are Archaea. We discovered several underwater fresh to brackish water springs in the Dead Sea harboring dense microbial communities. We provide the first characterization of these communities, discuss their possible origin, hydrochemical environment, energetic resources and the putative biogeochemical pathways they are mediating. Pyrosequencing of the 16S rRNA gene and community fingerprinting methods showed that the spring community originates from the Dead Sea sediments and not from the aquifer. Furthermore, it suggested that there is a dense Archaeal community in the shoreline pore water of the lake. Sequences of bacterial sulfate reducers, nitrifiers iron oxidizers and iron reducers were identified as well. Analysis of white and green biofilms suggested that sulfide oxidation through chemolitotrophy and phototrophy is highly significant. Hyperspectral analysis showed a tight association between abundant green sulfur bacteria and cyanobacteria in the green biofilms. Together, our findings show that the Dead Sea floor harbors diverse microbial communities, part of which is not known from other hypersaline environments. Analysis of the water’s chemistry shows evidence of microbial activity along the path and suggests that the springs supply nitrogen, phosphorus and organic matter to the microbial communities in the Dead Sea. The underwater springs are a newly recognized water source for the Dead Sea. Their input of microorganisms and nutrients needs to be considered in the assessment of possible impact of dilution events of the lake surface waters, such as those that will occur in the future due to the intended establishment of the Red Sea−Dead Sea water conduit.
Ion channels in the regulation of autophagy

ABSTRACT Autophagy is a cellular process in which the cell degrades and recycles its own constituents. Given the crucial role of autophagy in physiology, deregulation of autophagic machinery is associated with various diseases. Hence, a thorough understanding of autophagy regulatory mechanisms is crucially important for the elaboration of efficient treatments for different diseases. Recently, ion channels, mediating ion fluxes across cellular membranes, have emerged as important regulators of both basal and induced autophagy. However, the mechanisms by which specific ion channels regulate autophagy are still poorly understood, thus underscoring the need for further research in this field. Here we discuss the involvement of major types of ion channels in autophagy regulation.
Aerobic Interval Training Prevents Age-Dependent Vulnerability to Atrial Fibrillation in Rodents

Aims: Increasing age is the most important risk factor for atrial fibrillation (AF). Very high doses of exercise training might increase AF risk, while moderate levels seem to be protective. This study aimed to examine the effects of age on vulnerability to AF and whether long-term aerobic interval training (AIT) could modify these effects. Methods: Nine months old, male Sprague-Dawley rats were randomized to AIT for 16 weeks (old-ex) or to a sedentary control group (old-sed), and compared to young sedentary males (young-sed). After the intervention, animals underwent echocardiography, testing of exercise capacity (VO2max), and electrophysiology with AF induction before ex vivo electrophysiology. Fibrosis quantification, immunohistochemistry and western blotting of atrial tissue were performed. Results: Sustained AF was induced in vivo in 4 of 11 old-sed animals, but none of the old-ex or young-sed rats (p = 0.006). VO2max was lower in old-sed, while old-ex had comparable results to young-sed. Fibrosis was increased in old-sed (p = 0.006), with similar results in old-ex. There was a significantly slower atrial conduction in old-sed (p = 0.038), with an increase in old-ex (p = 0.027). Action potential duration was unaltered in old-sed, but prolonged in old-ex (p = 0.036). There were no differences in amount of atrial connexin 43 between groups, but a lateralization in atrial cardiomyocytes of old-sed, with similar findings in old-ex. Conclusion: AF vulnerability was higher in old-sed animals, associated with increased atrial fibrosis, lateralization of connexin-43, and reduced atrial conduction velocity. AIT reduced the age-associated susceptibility to AF, possibly through increased conduction velocity and prolongation of action potentials.
Regulation of Phosphatase and Tensin Homolog Expression and Activity by Transforming Growth-Factor Beta in the Trabecular Meshwork Cells: Implications for Primary Open Angle Glaucoma

Glaucoma is a multifactorial condition caused, in part, by fibrosis of the sieve-like trabecular meshwork (TM) tissue, which impedes drainage of aqueous humor (AH), leading to increased intraocular pressure and associated optic nerve damage and blindness. Fibrosis of the TM is mainly caused by the increased levels of active transforming growth factor-β 2 (TGFβ2) in the AH of glaucoma patients. Previous reports have shown that TGFβ decreases the expression of Phosphatase and Tensin Homolog (PTEN) gene and that PTEN is a major regulator of ECM deposition. In this study we investigate the regulation of PTEN protein expression and activity by TGFβ2 in TM cells to determine the mechanism by which excess ECM is deposited. Here we show that TGFβ2 induces collagen deposition in TM cells by phosphorylation of PTEN, a mechanism that is known to inactivate PTEN. Phosphorylation of PTEN by TGFβ is novel and has not been previously reported. We have found that PTEN protein expression and phosphorylation is regulated by the PI3 kinase pathway. We further show that transfection of TM cells to express enhanced-active PTEN decreases TGFβ2-induced expression of collagen type I (COL1) protein. Thus, regulation of PTEN activity could serve as a therapeutic target with high potential to prevent excess ECM deposition in the TM of glaucoma patients.