Miracle-dz/UniFAR-FTUs huggingface dataset:
TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population

Tumour necrosis factor (TNF)‐mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction–restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23–2.12), irrespective of sex and carriage of the major MS risk allele HLA‐DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71–2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex‐ and HLA‐DRB1*15:01‐independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.
Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Heart is the most active and incumbent organ of the body, which maintains blood flow, but due to various pathological reasons, several acute and chronic cardiac complications arise out of which myocardial infarction is one of the teething problems. Isoproterenol (ISP)‐induced myocardial ischemia is a classical model to screen the cardioprotective effects of various pharmacological interventions. Phytochemicals present a novel option for treating various human maladies including those of the heart. A large number of plant products and their active ingredients have been screened for efficacy in ameliorating ISP‐induced myocardial ischemia including coriander, curcumin, Momordica, quercetin, and Withania somnifera. These phytochemicals constituents may play key role in preventing disease and help in cardiac remodeling. Reactive oxygen species scavenging, antiinflammatory, and modulation of various molecular pathways such as Nrf2, NFкB, p‐21 activated kinase 1 (PAK1), and p‐smad2/3 signaling modulation have been implicated behind the claimed protection. In this review, we have provided a focused overview on the utility of ISP‐induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis for preclinical research. In addition, we have also surveyed molecular mechanism of various plant‐based interventions screened for cardioprotective effect in ISP‐induced cardiotoxicity, and their probable mechanistic profile is summarized.
Effects of connective tissue growth factor on prostate cancer bone metastasis and osteoblast differentiation

Previous studies have demonstrated that connective tissue growth factor (CTGF) is expressed at increased levels in prostate cancer bone metastasis mouse models and patients with prostate cancer which metastasizes to the bone; however, the underlying molecular mechanism(s) remain unknown. The present study investigated the function of CTGF in osteoblast differentiation and its effect on prostate cancer bone metastasis by analyzing CTGF gene expression and transcription at different levels of invasion, metastasis of prostate cancer cells, and the influence of CTGF on proliferation and xenotransplantation. A mouse model demonstrating bone metastasis was used to investigate the function(s) of CTGF in bone metastasis and osteoblast differentiation. Results demonstrated that CTGF expression was increased in association with high bone metastasis in prostate cancer cells, and its expression was significantly decreased in whole cell lysates. CTGF expression in prostate cancer cells with high levels of bone metastasis was increased 1.9-fold compared with prostate cancer cells with low levels of bone metastasis. The expression of CTGF in mesenchymal cells was markedly increased compared with epithelial cells. Results indicated that the increased expression of CTGF does not affect the proliferation of tumor cells and possesses no influence on tumor volume. Control and CTGF plasmids were transfected into RM1 cells and led to 4 and 17% bone lesions, respectively. Increased expression of CTGF significantly enlarged the tumor area in the bone metastatic position compared with the control. Positive areas of alkaline phosphatase were significantly decreased as the concentration of CTGF increased. The results of the present study demonstrated that CTGF promotes prostate carcinoma to metastasize in the bone by dysregulating osteoblast differentiation.
Differential Relationships of Guilt and Shame on Posttraumatic Stress Disorder Among Veterans

Objective: Despite important conceptual differences between shame and guilt, literature distinguishing these emotions in relation to posttrauma functioning for veterans has been largely theoretical. This is the first study to concurrently examine trauma-related guilt and internalized shame in relation to PTSD severity as the dependent variable. Our primary aim was to examine guilt and shame on PTSD symptom severity within the same model. A secondary aim was to evaluate whether trauma-related guilt can occur independent of shame. Method: Participants were 144 veterans seeking PTSD treatment. Regression analysis was used for our primary aim. Chi-square was used for our secondary aim to examine the percentage of participants categorized one standard deviation above (high) and below (low) the mean for shame and guilt. Results: Entered together, internalized shame (&bgr; = .44, p < .001) and guilt-related distress (&bgr; = .32, p < .001) were related to PTSD severity. Guilt cognitions and global guilt were unrelated to PTSD. Analyses showed significant differences in participants categorized as low/high shame and low/high global guilt (&khgr;2 = 14.22, p < .001), guilt-related distress (&khgr;2 = 15.09, p < .001), and guilt cognitions (&khgr;2 = 13.16, p < .001). Across guilt subscales, “shame-free” trauma-related guilt did not exist (0%). Conclusions Internalized shame and guilt distress were both related to PTSD severity; however, shame added variance not already accounted for by guilt. Tangney, Stuewig, and Mashek (2007) stipulate that guilt becomes maladaptive when fused with shame; however, our results indicate trauma-related guilt is possibly always fused with shame.
Testing Formal Predictions of Neuroscientific Theories of ADHD With a Cognitive Model–Based Approach

Neuroscientific theories of attention-deficit/hyperactivity disorder (ADHD) alternately posit that cognitive aberrations in the disorder are due to acute attentional lapses, slowed neural processing, or reduced signal-to-noise ratios. However, they make similar predictions about behavioral summary statistics (response times [RTs] and accuracy), hindering the field’s ability to produce strong and specific tests of these theories. The current study uses the linear ballistic accumulator (LBA; Brown & Heathcote, 2008), a mathematical model of choice RT tasks, to distinguish between competing theory predictions. Children with ADHD (n = 80) and age-matched controls (n = 32) completed a numerosity discrimination paradigm at 2 levels of difficulty, and RT data were fit to the LBA model to test theoretical predictions. Individuals with ADHD displayed slowed processing of evidence for correct responses (signal) relative to their peers but comparable processing of evidence for error responses (noise) and between-trial variability in processing (performance lapses). The findings are inconsistent with accounts that posit an increased incidence of attentional lapses in the disorder and provide partial support for those that posit slowed neural processing and lower signal-to-noise ratios. Results also highlight the utility of well-developed cognitive models for distinguishing between the predictions of etiological theories of psychopathology.
Analysis of corpus callosum size depending on age and sex.

BACKGROUND The aim of the study was to analyse changes in the size of the corpus callosum (CC) depending on age and sex and to establish the reference values of the morphometric indices of the CC in the Polish population. MATERIAL AND METHODS The results of MR studies of 1108 patients performed in the years 2010-2014 were analysed. Two independent radiologists evaluated cerebral images to exclude deviations from normal state. In patients divided according to sex and to 10 age groups, measurements of CC and brain dimensions were made and morphometric indices were calculated. RESULTS The results of measurements related to the following parameters: lengths of longitudinal cross-section of CC (CD), CC thickness in the narrowest place - isthmus (EF), the largest linear dimension of the brain from the frontal pole to the occipital pole (AB), the longitudinal cross-section area of the CC (A1) and cerebral cross-section area (A2) as well as CD/AB and A1/A2 ratios are summarized in 7 figures and 3 tables. CONCLUSIONS It was demonstrated, that in all age groups there are statistically significant differences in the values of the analysed parameters and ratios of CC size. It was indicated, that there are no statistically significant differences between men and women in the CD, EF, and A1 parameters related to CC size, and the profiles of variations of these parameters are very similar. It was proved that there are statistical differences between women and men in parameters/indicators concerning of the brain size.
A Novel Differential Ion Mobility Device Expands the Depth of Proteome Coverage and the Sensitivity of Multiplex Proteomic Measurements*

The depth of proteomic analyses is often limited by the overwhelming proportion of confounding background ions that compromise the identification and quantification of low abundance peptides. To alleviate these limitations, we present a new high field asymmetric waveform ion mobility spectrometry (FAIMS) interface that can be coupled to the Orbitrap Tribrid mass spectrometers. The interface provides several advantages over previous generations of FAIMS devices, including ease of operation, robustness, and high ion transmission. Replicate LC-FAIMS-MS/MS analyses (n = 100) of HEK293 protein digests showed stable ion current over extended time periods with uniform peptide identification on more than 10,000 distinct peptides. For complex tryptic digest analyses, the coupling of FAIMS to LC-MS/MS enabled a 30% gain in unique peptide identification compared with non-FAIMS experiments. Improvement in sensitivity facilitated the identification of low abundance peptides, and extended the limit of detection by almost an order of magnitude. The reduction in chimeric MS/MS spectra using FAIMS also improved the precision and the number of quantifiable peptides when using isobaric labeling with tandem mass tag (TMT) 10-plex reagent. We compared quantitative proteomic measurements for LC-MS/MS analyses performed using synchronous precursor selection (SPS) and LC-FAIMS-MS/MS to profile the temporal changes in protein abundance of HEK293 cells following heat shock for periods up to 9 h. FAIMS provided 2.5-fold increase in the number of quantifiable peptides compared with non-FAIMS experiments (30,848 peptides from 2,646 proteins for FAIMS versus 12,400 peptides from 1,229 proteins with SPS). Altogether, the enhancement in ion transmission and duty cycle of the new FAIMS interface extended the depth and comprehensiveness of proteomic analyses and improved the precision of quantitative measurements.
“Taking responsibility for my health”: Health system barriers and women’s attitudes toward cervical cancer screening in Romania and Bulgaria

The study used mixed-methods to illustrate the complexity of the interplay between the contexts in Bulgaria and Romania and women’s attitudes and behaviors related to screening. A secondary analysis of quantitative data from Romanian (n = 1053) and Bulgarian (n = 1099) women and qualitative interviews (n = 30 Romanian, n = 35 Bulgarian) was performed. Low rates of screening attendance were found in both countries. Regression analysis illustrates that attitudes and social norms significantly predicted intentions and screening behavior in both countries. Thematic analysis revealed that systemic barriers and cultural meanings were relevant to women’s decisions to attend screening or avoid contact with the health-care system.
Species- and C-terminal linker-dependent variations in the dynamic behavior of FtsZ on membranes in vitro

Bacterial cell division requires the assembly of FtsZ protofilaments into a dynamic structure called the ‘Z-ring’. The Z-ring recruits the division machinery and directs local cell wall remodeling for constriction. The organization and dynamics of protofilaments within the Z-ring coordinate local cell wall synthesis during cell constriction, but their regulation is largely unknown. The disordered C-terminal linker (CTL) region of Caulobacter crescentus FtsZ (CcFtsZ) regulates polymer structure and turnover in solution in vitro, and regulates Z-ring structure and activity of cell wall enzymes in vivo. To investigate the contributions of the CTL to the polymerization properties of FtsZ on its physiological platform, the cell membrane, we reconstituted CcFtsZ polymerization on supported lipid bilayers (SLB) and visualized polymer dynamics and structure using total internal reflection fluorescence microscopy. Unlike E. coli FtsZ protofilaments that organized into large, bundled patterns, CcFtsZ protofilaments assembled into small, dynamic clusters on SLBs. Moreover, CcFtsZ lacking its CTL formed large networks of straight filament bundles that underwent slower turnover than the dynamic clusters of wildtype FtsZ. Our in vitro characterization provides novel insights into species- and CTL-dependent differences between FtsZ assembly properties that are relevant to Z-ring assembly and function on membranes in vivo.
Regional variation in drivers of connectivity for two frog species (Rana pretiosa and R. luteiventris) from the U.S. Pacific Northwest

Comparative landscape genetics has uncovered high levels of variability in which landscape factors affect connectivity among species and regions. However, the relative importance of species traits versus environmental variation for predicting landscape patterns of connectivity is unresolved. We provide evidence from a landscape genetics study of two sister taxa of frogs, the Oregon spotted frog (Rana pretiosa) and the Columbia spotted frog (Rana luteiventris) in Oregon and Idaho, USA. Rana pretiosa is relatively more dependent on moisture for dispersal than R. luteiventris, so if species traits influence connectivity, we predicted that connectivity among R. pretiosa populations would be more positively associated with moisture than R. luteiventris. However, if environmental differences are important drivers of gene flow, we predicted that connectivity would be more positively related to moisture in arid regions. We tested these predictions using eight microsatellite loci and gravity models in two R. pretiosa regions and four R. luteiventris regions (n = 1,168 frogs). In R. pretiosa, but not R. luteiventris, connectivity was positively related to mean annual precipitation, supporting our first prediction. In contrast, connectivity was not more positively related to moisture in more arid regions. Various temperature metrics were important predictors for both species and in all regions, but the directionality of their effects varied. Therefore, the pattern of variation in drivers of connectivity was consistent with predictions based on species traits rather than on environmental variation.
Dynamics of the Pollen Sequestrome Defined by Subcellular Coupled Omics1[OPEN]

The pollen sequestrome is found to be a highly dynamic compartment for the storage of translationally repressed mRNAs, and nontranslating monosomes are proposed to be the primary mediators of mRNA sequestration in Nicotiana tabacum. Reproduction success in angiosperm plants depends on robust pollen tube growth through the female pistil tissues to ensure successful fertilization. Accordingly, there is an apparent evolutionary trend to accumulate significant reserves during pollen maturation, including a population of stored mRNAs, that are utilized later for a massive translation of various proteins in growing pollen tubes. Here, we performed a thorough transcriptomic and proteomic analysis of stored and translated transcripts in three subcellular compartments of tobacco (Nicotiana tabacum), long-term storage EDTA/puromycin-resistant particles, translating polysomes, and free ribonuclear particles, throughout tobacco pollen development and in in vitro-growing pollen tubes. We demonstrated that the composition of the aforementioned complexes is not rigid and that numerous transcripts were redistributed among these complexes during pollen development, which may represent an important mechanism of translational regulation. Therefore, we defined the pollen sequestrome as a distinct and highly dynamic compartment for the storage of stable, translationally repressed transcripts and demonstrated its dynamics. We propose that EDTA/puromycin-resistant particle complexes represent aggregated nontranslating monosomes as the primary mediators of messenger RNA sequestration. Such organization is extremely useful in fast tip-growing pollen tubes, where rapid and orchestrated protein synthesis must take place in specific regions.
Quantitative Assessment of the Effect of the Out-of-Plane Movement of the Homogenous Ellipsoidal Model of the Left Ventricle on the Deformation Measures Estimated Using 2-D Speckle Tracking—An In-Silico Study

Effect of the out-of-plane (OOP) movement amplitude on estimates of global displacements (radial, circumferential) and strains (radial <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {R}}$ </tex-math></inline-formula>, circumferential <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {C}}$ </tex-math></inline-formula>) was studied in an ellipsoidal model of the left ventricle using finite-element modeling (FEM), synthetic ultrasonic data, and short-axis view. This effect was assessed using median of the absolute relative error (RE) of the global parameters. FEM provided node displacements for synthetic ultrasonic data and reference data generation. Displacements were estimated using block-matching (BM) and B-spline (BS) methods. FEM-derived data analysis, free from errors resulting from speckle tracking, indicated that the tissue motion introduced REs of global strain estimates below 4.5%. The effect of the OOP motion amplitude on strain estimates was strain specific and depended on the displacement estimation method. In the case of <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {C}}$ </tex-math></inline-formula>, the increase of the OOP amplitude resulted in quasi-linear increase of the RE from approximately 10% to 15%. The modulus of the end-systolic (ES) errors of the <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {C}}$ </tex-math></inline-formula> estimates almost linearly increased with increasing OOP amplitude approximately from 10% to 16%. REs of the <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {R}}$ </tex-math></inline-formula> estimate were close to 80% and 40%, respectively, in the case of the BM and BS methods, and increased with increasing OOP amplitude. The modulus of the ES errors of the <inline-formula> <tex-math notation="LaTeX">$\varepsilon _{\mathrm {R}}$ </tex-math></inline-formula> estimates in the case of the BS method was about −40% and showed low sensitivity to the OOP amplitude; in the BM case, these errors varied approximately from −70% to −58% for OOP amplitude from 0 to 15 mm.
Study of Adverse Drug Effects of Direct-Acting Antivirals for Chronic HCV Infection at Fayoum Governorate, Egypt - A Pharmacovigilance Study.

BACKGROUND Different combinations of Direct Antiviral Agents (DAAs) have been used against different Hepatitis C Virus (HCV) genotypes and in different types of patients. Despite being effective and characterized by a very low rate of adverse effects in clinical trials, few data are available on adverse events in real life studies. OBJECTIVES The aim of this study was to identify the incidence and pattern of Adverse Drug Reactions (ADRs) caused by DAAs; daclatasvir and sofosbuvir and their combination with ribavirin and to assess the causality and the severity of the reported ADRs. METHODS A prospective observational study was conducted over six months at treatment HCV center of Health Insurance Hospital in Fayoum Governorate, Egypt. A pre-tested, interviewed structured questionnaire was used by authors to gather required data from 345 enrolled patients regarding demographics, co-morbidity and ADRs. Causality and severity of ADRs were assessed. RESULTS According to our data. we have found that 75.7% (261out of 345) patients reported 36 different ADRs involving different systems, of these 1.2% experienced Serious Adverse Events (SAEs), including three deaths (0.9%). A majority of ADRs were more significantly reported with ribavirin-containing regimen. Out of 345 patients, 23.5% have comorbidities. Among them, 92.6% reported ADRs. Causality assessment of ADRs by WHO-UMC criteria revealed that 38.89% were probable while 61.11% were possible. CONCLUSION New antiviral drugs require careful follow-up of any significant adverse event that may occur and can affect adherence. Special population as the elderly and those with comorbidities should always be managed with caution to avoid development of serious side effects.
MiR-1256 suppresses proliferation and migration of non-small cell lung cancer via regulating TCTN1

Mounting evidence has shown that miRNA expression is abnormal in various human cancers. Here, we mainly explored the biological function and the potential mechanisms of miR-1256 in non-small cell lung cancer (NSCLC). The miR-1256 mRNA expression was detected by quantitative real-time PCR and tectonic family member 1 (TCTN1) mRNA expression was detected by immunoblotting. The TCTN1 was identified to be the direct and specific target gene of miR-1256 by luciferase reporter assay. Cell proliferation was examined by methyl thiazolyl tetrazolium assay and migration was detected by transwell assay. MiR-1256 expression was downregulated in NSCLC tissues, whereas the expression of TCTN1 was upregulated, compared with normal tissues. We also found that overexpression of miR-1256 in these NSCLC cell lines inhibited cell proliferation and migration. Furthermore, TCTN1 was identified as a direct target of miR-1256 by luciferase reporter assays. Collectively, these data stated that the inhibitory effect of miR-1256 in NSCLC was realized by upregulating TCTN1, suggesting that miR-1256/TCTN1 axis may play a critical role as NSCLC therapeutic target.