Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid brain responses to affective pictures indicate dimensions of trauma‐related psychopathology in adolescents

Abstract A variety of mental disorders are related to deviant brain activity, but these neural alterations do not validate psychiatric diagnostic categories. High symptom overlap and variable symptom patterns encourage a dimensional approach. Following the logic of the Research Domain Criteria (RDoC), we investigated trauma survivors for symptom clusters that might be associated with characteristics of ERPs, in particular with the early posterior negativity (EPN) elicited during affective picture processing. In rapid serial visual presentation, 90 adolescents (40 male/50 female, age M = 15.0 ± 2.5 years) who had been exposed to varying amounts of traumatic stress passively viewed a stream of high‐arousing positive and low‐arousing neutral pictures taken from the International Affective Picture System (IAPS). Using standardized interviews, symptoms of trauma‐related mental disorders were assessed (including those for PTSD, depression, borderline personality disorder, and behavioral problems). A principal component analysis was performed to derive potential dimensions of psychopathology. Multiple regression analysis confirmed a factor comprising problems concentrating, sleeping difficulties, and mistrust as a predictor of a larger EPN difference between high‐arousing positive and low‐arousing neutral IAPS pictures (β = 0.19, p < 0.05). Sex predicted the magnitude of the EPN (β = 0.45, p < 0.001). Male adolescents displayed a stronger EPN suppression than female adolescents. The result suggests that problems concentrating, sleeping difficulties, and mistrust seem to be trans‐diagnostic elements related to diminished early emotional discrimination represented by the EPN. Furthermore, our findings indicate that the EPN in response to emotional processing is modulated by sex.
Pharmacogenetic Analysis of the UK MRC (Medical Research Council) MAGIC Trial: Association of Polymorphisms with Toxicity and Survival in Patients Treated with Perioperative Epirubicin, Cisplatin, and 5-fluorouracil (ECF) Chemotherapy

Purpose: Germline polymorphisms may affect chemotherapy efficacy and toxicity. We examined the effect of polymorphisms in drug metabolism and DNA repair genes on pathologic response rates, survival, and toxicity for patients randomized to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. Experimental Design: DNA was extracted from nontumor resection formalin-fixed paraffin-embedded (FFPE) blocks. ERCC1, ERCC2, XRCC1, DYPD, and OPRT SNPs were evaluated using Sequenom, GSTP1, GSTT1 deletion, and TYMS (TS) 5′ 2R/3R using multiplex PCR. Post PCR amplification, TS 2R/3R and GSTT1 samples underwent gel electrophoresis. Results: Polymorphism data were available for 289 of 456 (63.4%) operated patients. No polymorphism was statistically significantly associated with pathologic response to chemotherapy. Median overall survival (OS) for patients treated with surgery alone with any TS genotype was not different (1.76 years 2R/2R, 1.68 years 2R/3R, 2.09 years 3R/3R). Median OS for patients with a TS 2R/2R genotype treated with chemotherapy was not reached, whereas median OS for 2R/3R and 3R/3R patients were 1.44 and 1.60 years, respectively (log rank P value = 0.0053). The P value for the interaction between treatment arm and genotype (3R/3R and 3R/2R vs. 2R/2R) was 0.029. No polymorphism was statistically significantly associated with chemotherapy toxicity. Conclusions: In MAGIC, patients with a TS 2R/2R genotype appeared to derive a larger benefit from perioperative ECF chemotherapy than patients with 3R containing genotypes. Further exploration of this potential predictive biomarker in this patient population is warranted. Clin Cancer Res; 23(24); 7543–9. ©2017 AACR.
Perceived Barriers to Mammography Adoption among Women in Iran: A Qualitative Study

Background Breast cancer is the most commonly diagnosed tumorous cancer and the second leading cause of cancer-related deaths among women worldwide. This study aimed to qualitatively explore the barriers to mammography adoption among Iranian women. Methods This study is a qualitative component of a large research project on exploratory sequential mixed method design, utilizing conventional content analysis. In total, 24 participants were selected from among women who had participated in the first phase of the study. Data were collected through in-depth, semi-structured interviews. Results Five main themes were extracted, consisting of unawareness of mammography, fear control, priority of mammography needs, inadequate competency of mammography centers, and a sense of losing family support. Conclusion Different perceived barriers within various levels (individual, intrapersonal, health systems, and community) play influential roles in women’s decisions to participate in breast cancer screening program, which indicates the cultural aspect of perceived barriers in different communities and countries. The study provides the basis for intervention planning in this regard.
HLA, Non-HLA Antibodies, and Eplet Mismatches in Pediatric Liver Transplantation: Observations From a Small, Single-Center Cohort.

OBJECTIVES To identify the risk of developing acute rejection, allograft fibrosis, and antibody-mediated rejection, a retrospective review of pediatric patients who underwent liver transplant between July 31, 1998 and February 29, 2016 and had donor-specific antibodies measured at time of liver biopsy was undertaken. MATERIALS AND METHODS HLAMatchmaker Software (http://www.hlamatchmaker.net) was used to define epitope mismatches between donors and recipients and to predict de novo donor-specific antibody risk. Epitope mismatches were evaluated for their immunogenicity. RESULTS In our group of 42 recipients, 20 (48%) had donor-specific antibodies. Having an antibody against HLA-DQB1*02 was associated with acute rejection (66.6% vs 36%; P = .024). We found that DQ epitope mismatch load was greater in recipients with class II donor-specific antibodies (9.7 vs 3.6; P = .001). HLA-DQ (7.4 vs 3.6; P = .04) and HLA-DR (8.8 vs 3.8; P = .04) epitope mismatch loads were higher in recipients with DQ + DR donor-specific antibodies. A high portal fibrosis score was associated with higher mismatch load at the DQ locus (P = .005) and DQ + DR loci (P = .03). Having > 5 or > 6 epitope mismatch loads at the DQ locus identified a threshold above which development of DQ donor-specific antibodies would occur (area under the curve = 0.878). Mismatches for eplet 4Q, 45GE, 52PQ, and 52PL, thought to be immunodominant epitopes, were observed for several recipients. CONCLUSIONS Knowledge of epitope mismatches between recipients and donors may aid transplant physicians in devising immunosuppression strategies.
Assessment of Microcirculatory Remodeling With Intracoronary Flow Velocity and Pressure Measurements: Validation With Endomyocardial Sampling in Cardiac Allografts

Background— Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. Methods and Results— In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13±0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33±1.25 cm · s · −1mm Hg−1), coronary resistance index (1.65±0.88 mm Hg · cm−1 · s−1), and coronary resistance reserve (2.36±0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57±6.95%) and density (2.00±1.22 arterioles per 1 mm2) and capillary density (645±179 capillaries per 1 mm2) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (&bgr;=0.61, P=0.0009) and capillary density (&bgr;=−0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. Conclusions— Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently.
Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts

Although hypoxia is known to contribute to several aspects of tumour progression, relatively little is known about the effects of hypoxia on cancer-associated myofibroblasts (CAMs), or the consequences that conditional changes in CAM function may have on tumour development and metastasis. To investigate this issue in the context of gastric cancer, a comparative multiomic analysis was performed on populations of patient-derived myofibroblasts, cultured under normoxic or hypoxic conditions. Data from this study reveal a novel set of CAM-specific hypoxia-induced changes in gene expression and secreted proteins. Significantly, these signatures are not observed in either patient matched adjacent tissue myofibroblasts (ATMs) or non-cancer associated normal tissue myofibroblasts (NTMs). Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts.
A novel score in the prediction of rhythm outcome after ablation of atrial fibrillation: The SUCCESS score

Objective: The aim of the present study was to assess the predictive value of the CHADS2, CHA2DS2-VASc, R2CHADS2, and APPLE scores for rhythm outcome in patients with atrial fibrillation (AF) after catheter ablation. Methods: The cohort of the present study consisted of 192 patients with AF who underwent a total of 265 ablations. Rhythm outcome was documented between 3 and 24 month after ablation. The mentioned scores were calculated for every patient. Results: Of the patients, 139 (72%) were successfully treated having freedom of any atrial tachyarrhythmia, whereas 21 (11%) had partial success, and 32 (17%) had failure. For univariate analysis, the APPLE score was the only significant predictor of outcome after ablation with an odds ratio (OR) of 1.485 [95% confidence interval (CI) 1.075–2.052, p-value 0.017]. A multivariate binary regression corrected for possible confounders showed that the APPLE score (OR 1.527, 95% CI 1.082–2.153, p-value 0.016) along with the number of previous ablations (OR 5.831, 95% CI 1.356–25.066, p-value 0.018) is a significant predictor of outcome. A novel score (SUCCESS) was created by adding one point to the APPLE score for each previously performed ablation. This novel score demonstrated an improvement in receiver operating characteristic curve analysis (area under the curve 0.657 vs. 0.620). However, these findings were not significant in our study (p-value 0.219). Conclusion: Both the APPLE and the novel SUCCESS scores are superior to the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores in predicting AF recurrence after catheter ablation. The SUCCESS score appears to have a higher predictive value than the APPLE score and might be a valuable tool to estimate the risk of AF recurrence in patients eligible for catheter ablation.
Microencapsulation of antioxidant phenolic compounds from green coffee

Abstract Green coffee is a prime source of antioxidants to functional food and nutraceuticals. Arabica and Robusta varieties were screened and decaffeinated using ethyl lactate and extracted with a polar solvent to obtain chlorogenic acid (CGA) enriched green coffee extract (GCE). The physicochemical qualities (moisture, pH, particle size, and color) and bioactive compounds (total phenolics, chlorogenic acid, and caffeine) of GCE were assessed. The GCE had 12.78 ± 2.1 mg GAE g−1 phenolics and 10.98 mg g−1 chlorogenic acid (CGA). To improve the stability of CGA, the GCE encapsulated by spray drying using maltodextrin (MD) and skim milk (SM) as coating agent individually and in combination. Physicochemical, antioxidant properties, and biofunctionalities of microparticles were evaluated. Highest encapsulation efficiency of GCE with maltodextrin (1:1) was 86%±3 with the smaller particle size (2.3 ± 0.1 µm). Under the simulated gastric juice and bile salts solution, microencapsulation provided significantly better protection compared to non-encapsulated GCE. MGE elicits use as adjuvant/supplements in food, fortified for nutraceuticals and pharmaceuticals.
Parents with intellectual disabilities and their perspective of peer support: "It depends on how they give it".

BACKGROUND Parents with intellectual disabilities face particular challenges, such as lack of sufficient support with their parenting. Peers can be an important source of support for parents in the general population; however, there is a limited knowledge about peer support for parents with intellectual disabilities. The aim of this study was to explore experiences of parents with intellectual disabilities with social support with a focus on the role of peers. METHOD Twenty-six parents with intellectual disabilities in New South Wales, Australia, took part in a semi-structured interview. RESULTS The inductive content analysis of data revealed three main themes; this article reports on one of them-Developing interdependence. CONCLUSIONS The source of support was less important than the way support was offered. Parents valued support offered by someone who respected them as a person and parent, and was interested in what they wanted and needed.
Genome-Wide Comparative Analyses of Polyadenylation Signals in Eukaryotes Suggest a Possible Origin of the AAUAAA Signal

Pre-mRNA cleavage and polyadenylation is an essential step for almost all mRNA in eukaryotes. The cis-elements around the poly(A) sites, however, are very diverse among different organisms. We characterized the poly(A) signals of seven different species, and compared them with that of four well-studied organisms. We found that ciliates do not show any dominant poly(A) signal; a triplet (UAA) and tetramers (UAAA and GUAA) are dominant in diatoms and red alga, respectively; and green alga Ostreococcus uses UGUAA as its poly(A) signal. Spikemoss and moss use conserved AAUAAA signals that are similar to other land plants. Our analysis suggests that the first two bases (NN in NNUAAA) are likely degenerated whereas UAAA appears to be the core motif. Combined with other published results, it is suggested that the highly conserved poly(A) signal AAUAAA may be derived from UAA with an intermediate, putative UAAA, following a pathway of UAA→UAAA→AAUAAA.
An updated phylogeny of the Alphaproteobacteria reveals that the parasitic Rickettsiales and Holosporales have independent origins

The Alphaproteobacteria is an extraordinarily diverse and ancient group of bacteria. Previous attempts to infer its deep phylogeny have been plagued with methodological artefacts. To overcome this, we analyzed a dataset of 200 single-copy and conserved genes and employed diverse strategies to reduce compositional artefacts. Such strategies include using novel dataset-specific profile mixture models and recoding schemes, and removing sites, genes and taxa that are compositionally biased. We show that the Rickettsiales and Holosporales (both groups of intracellular parasites of eukaryotes) are not sisters to each other, but instead, the Holosporales has a derived position within the Rhodospirillales. A synthesis of our results also leads to an updated proposal for the higher-level taxonomy of the Alphaproteobacteria. Our robust consensus phylogeny will serve as a framework for future studies that aim to place mitochondria, and novel environmental diversity, within the Alphaproteobacteria.
Neuroprotective Effects of Combined Treatment with Minocycline and Olfactory Ensheathing Cells Transplantation against Inflammation and Oxidative Stress after Spinal Cord Injury

Objective Traumatic spinal cord injury (SCI) is considered one of the most devastating injuries leading to neuronal disruption. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In this study, we have tested the efficacy of combined treatment with minocycline and OECs after contusive spinal cord injury. Materials and Methods In this experimental study, adult female Wistar rats were randomly divided into five groups. Rats received an intraperitoneal injection of minocycline immediately after SCI, and then 24 hours after the injury. Transplantations were performed 7 days after the injury. Functional recovery was evaluated using the Basso, Beattie and Bresnahan scale (BBB). After that, the animals were sacrificed, and T11 segment of the spinal cord was removed after 5 weeks, and then used for histopathological, immunohistochemical, and biochemical assessments. Western blot analysis was applied to determine the protein expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL1β) and caspase3. Results The results of this study showed that the combination of OECs graft and minocycline reduced the functional deficits and diminished cavitation and astrogliosis in spinal tissue. The analysis of protein expression by western blotting revealed that minocycline treatment along with OECs transplantation further decreased the level of IL-1β, TNF-α, caspase-3, and the oxidative stress as compared with when minocycline or OECs transplantation was used alone. Conclusion The combinatory treatment with OECs graft and minocycline induced a more effective response to the repair of spinal cord injury, and it is considered a therapeutic potential for the treatment of SCI.
Cytotoxic Activity of the Histone Deacetylase 3-Selective Inhibitor Pojamide on MDA-MB-231 Triple-Negative Breast Cancer Cells

We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 μM concentration caused an approximate halving of cell number after 24 h of exposure, whereas the tetrafluoroborate derivative exerted no effect on cell survival nor proliferation. Flow cytometric and protein blot analyses were performed on cells exposed to both Pojamide and the ferrocenyladipamide derivative to evaluate cell cycle distribution, apoptosis/autophagy modulation, and mitochondrial metabolic state in order to assess the cellular basis of the cytotoxic effect. The data obtained show that the cytotoxic effect of the two deacetylase inhibitors may be ascribed to the onset of non-apoptotic cell death conceivably linked to a down-regulation of autophagic processes and an impairment of mitochondrial function with an increase in intracellular reactive oxygen species. Our work expands the list of autophagy-regulating drugs and also provides a further example of the role played by the inhibition of autophagy in breast cancer cell death. Moreover, the compounds studied may represent attractive and promising targets for subsequent molecular modeling for anti-neoplastic agents in malignant breast cancer.
ACE activity in blood and brain axis in an animal model for schizophrenia: Effects of dopaminergic manipulation with antipsychotics and psychostimulants

Abstract Objectives: Angiotensin I-converting enzyme (ACE) was initially correlated with schizophrenia (SCZ) in studies showing a correlation of ACE increased enzyme activity with memory impairments. Possible role for ACE in SCZ was also suggested by ACE activity interaction with dopaminergic mechanisms to modulate abnormalities of sensorimotor gating. In addition, we have demonstrated higher ACE activity in blood of SCZ subjects, its implication in cognitive performance in SCZ and its power as a predictor for SCZ diagnosis. Methods: ACE activity was determined in the serum and in selected brain regions of an animal model presenting SCZ-like behaviour, before and after the treatment with typical and atypical antipsychotics, and also in the serum of animals receiving the psychostimulants amphetamine/lisdexamphetamine. Results: Dopaminergic manipulations with antipsychotics and psychostimulants influenced the ACE activity, but with no correlation with the animal blood pressure. Conclusions: The validity of measuring ACE activity in animal blood to predict activity in the CNS, as well as the lack of correlation between the activity and blood pressure, before and after the treatment with antipsychotics, were confirmed here. Correlations of the present findings with data from clinical studies also strengthen the value of this animal model for studying several aspects of SCZ.
Contraction of atrial smooth muscle reduces cardiac output in perfused turtle hearts

ABSTRACT Unusual undulations in resting tension (tonus waves) were described in isolated atria from freshwater turtles more than a century ago. These tonus waves were soon after married with the histological demonstration of a rich layer of smooth muscle on the luminal side of the atrial wall. Research thereafter waned and the functional significance of this smooth muscle has remained obscure. Here, we provide evidence that contraction of the smooth muscle in the atria may be able to change cardiac output in turtle hearts. In in situ perfused hearts of the red-eared slider turtle (Trachemys scripta elegans), we demonstrated that activation of smooth muscle contraction with histamine (100 nmol kg−1 bolus injected into perfusate) reduced cardiac output by decreasing stroke volume (>50% decrease in both parameters). Conversely, inhibition of smooth muscle contraction with wortmannin (10 µmol l−1 perfusion) approximately doubled baseline stroke volume and cardiac output. We suggest that atrial smooth muscle provides a unique mechanism to control cardiac filling that could be involved in the regulation of stroke volume during diving. Summary: In the hearts of freshwater turtles, contraction of smooth muscle in the atria limits cardiac filling thereby decreasing cardiac output.