Miracle-dz/UniFAR-FTUs huggingface dataset:
Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes

Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro. Expression of soluble/immunoreactive activin-A and its receptors was measured in serum, bronchoalveolar lavage fluid (BALF) and endobronchial biopsies from 16 healthy controls, 19 patients with mild/moderate asthma and 22 severely asthmatic patients. In vitro effects of activin-A on baseline and vascular endothelial growth factor (VEGF)-induced human endothelial cell angiogenesis, signalling and cytokine release were compared with BALF concentrations of these cytokines in vivo. Activin-A expression was significantly elevated in serum, BALF and bronchial tissue of the asthmatics, while expression of its protein receptors was reduced. In vitro, activin-A suppressed VEGF-induced endothelial cell proliferation and angiogenesis, inducing autocrine production of anti-angiogenic soluble VEGF receptor (R)1 and interleukin (IL)-18, while reducing production of pro-angiogenic VEGFR2 and IL-17. In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis. Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo, where reduced basal expression of its receptors is observed particularly in severe asthma. Anti-angiogenic role of activin-A, overexpressed in severe asthma, may be compromised by reduced receptor signalling http://ow.ly/W4kxF
Small area estimation using a spatio-temporal linear mixed model

• In this paper it is proposed a spatio-temporal area level linear mixed model involving spatially correlated and temporally autocorrelated random effects. An empirical best linear unbiased predictor (EBLUP) for small area parameters has been obtained under the proposed model. Using previous research in this area, analytical and bootstrap estimators of the mean squared prediction error (MSPE) of the EBLUP have also been worked out. An extensive simulation study using time-series and cross-sectional data was undertaken to compare the efficiency of the proposed EBLUP estimator over other well-known EBLUP estimators and to study the properties of the proposed estimators of MSPE.
Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure Patients: Insights From Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION).

BACKGROUND Psychosocial factors may influence adherence with exercise training for heart failure (HF) patients. We aimed to describe the association between social support and barriers to participation with exercise adherence and clinical outcomes. METHODS AND RESULTS Of patients enrolled in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), 2279 (97.8%) completed surveys to assess social support and barriers to exercise, resulting in the perceived social support score (PSSS) and barriers to exercise score (BTES). Higher PSSS indicated higher levels of social support, whereas higher BTES indicated more barriers to exercise. Exercise time at 3 and 12 months correlated with PSSS (r= 0.09 and r= 0.13, respectively) and BTES (r=-0.11 and r=-0.12, respectively), with higher exercise time associated with higher PSSS and lower BTES (All P<0.005). For cardiovascular death or HF hospitalization, there was a significant interaction between the randomization group and BTES (P=0.035), which corresponded to a borderline association between increasing BTES and cardiovascular death or HF hospitalization in the exercise group (hazard ratio 1.25, 95% confidence interval 0.99, 1.59), but no association in the usual care group (hazard ratio 0.83, 95% confidence interval 0.66, 1.06). CONCLUSIONS Poor social support and high barriers to exercise were associated with lower exercise time. PSSS did not impact the effect of exercise training on outcomes. However, for cardiovascular death or HF hospitalization, exercise training had a greater impact on patients with lower BTES. Given that exercise training improves outcomes in HF patients, assessment of perceived barriers may facilitate individualized approaches to implement exercise training therapy in clinical practice. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials. gov. Unique identifier: NCT00047437.
Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. Methods: We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. Results: Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. Conclusions: COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population.
Qat Chewing and Periodontal Pathogens in Health and Disease: Further Evidence for a Prebiotic-Like Effect

Aim. Qat chewing has been reported to induce subgingival microbial shifts suggestive of prebiotic-like properties. The objective here was to assess the effect of qat chewing on a panel of classical and new putative periopathogens in health and periodontitis. Materials and Methods. 40 qat chewers and 40 nonchewers, equally stratified by periodontal health status, were recruited. Taqman, real-time PCR was used to quantify total bacteria, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Parvimonas micra, Filifactor alocis, Synergistetes, and TM7s in pooled subgingival biofilm samples. Differences in microbial parameters between the study groups were analysed using ordinal regression. Results. In health, the qat chewers harboured significantly lower relative counts of P. gingivalis, T. forsythia, Synergistetes, and TM7s after adjustment for multiple comparisons (P ≤ 0.007). At nominal significance level, they also carried lower counts of TM7s and P. micra (P ≤ 0.05). In periodontitis, the chewers had lower counts of all taxa; however, only T. denticola withstood correction for multiple comparisons (P ≤ 0.0063). Conclusions. Qat chewing is associated with lower proportions of periopathogens, particularly in subjects with healthy periodontium, which supports previous reports of its prebiotic-like properties. This potentially beneficial biological effect can be exploited by attempting to isolate the active fraction.
Mucoidy, Quorum Sensing, Mismatch Repair and Antibiotic Resistance in Pseudomonas aeruginosa from Cystic Fibrosis Chronic Airways Infections

Survival of Pseudomonas aeruginosa in cystic fibrosis (CF) chronic infections is based on a genetic adaptation process consisting of mutations in specific genes, which can produce advantageous phenotypic switches and ensure its persistence in the lung. Among these, mutations inactivating the regulators MucA (alginate biosynthesis), LasR (quorum sensing) and MexZ (multidrug-efflux pump MexXY) are the most frequently observed, with those inactivating the DNA mismatch repair system (MRS) being also highly prevalent in P. aeruginosa CF isolates, leading to hypermutator phenotypes that could contribute to this adaptive mutagenesis by virtue of an increased mutation rate. Here, we characterized the mutations found in the mucA, lasR, mexZ and MRS genes in P. aeruginosa isolates obtained from Argentinean CF patients, and analyzed the potential association of mucA, lasR and mexZ mutagenesis with MRS-deficiency and antibiotic resistance. Thus, 38 isolates from 26 chronically infected CF patients were characterized for their phenotypic traits, PFGE genotypic patterns, mutations in the mucA, lasR, mexZ, mutS and mutL gene coding sequences and antibiotic resistance profiles. The most frequently mutated gene was mexZ (79%), followed by mucA (63%) and lasR (39%) as well as a high prevalence (42%) of hypermutators being observed due to loss-of-function mutations in mutL (60%) followed by mutS (40%). Interestingly, mutational spectra were particular to each gene, suggesting that several mechanisms are responsible for mutations during chronic infection. However, no link could be established between hypermutability and mutagenesis in mucA, lasR and mexZ, indicating that MRS-deficiency was not involved in the acquisition of these mutations. Finally, although inactivation of mucA, lasR and mexZ has been previously shown to confer resistance/tolerance to antibiotics, only mutations in MRS genes could be related to an antibiotic resistance increase. These results help to unravel the mutational dynamics that lead to the adaptation of P. aeruginosa to the CF lung.
Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy

Purpose of review To provide an update on current management of retinoblastoma Recent findings The current major treatment strategies for retinoblastoma involve enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Enucleation is reserved for eyes with extensive retinoblastoma, in which there is no hope for useful vision. Newer implants following enucleation allow excellent cosmetic and motility outcome. Intravenous chemoreduction has been popular for nearly two decades and continues to provide favorable tumor control for most eyes classified as groups A, B, or C and some D eyes, using the International Classification of Retinoblastoma. Using chemoreduction, there has been an apparent reduction in the incidence of pinealoblastoma in children with germline mutation retinoblastoma. Intra-arterial chemotherapy involves single-agent injection into the ophthalmic artery under careful neurointerventional guidance. This recently popularized therapy can be useful for eyes that fail standard treatments or for some eyes as a primary treatment. Short-term results are favorable but longer follow-up is warranted. Summary Progress has been made in the past few years in the management of retinoblastoma with better enucleation implants, chemoreduction-prevention of pinealoblastoma and excellent tumor control, and we face the recently popularized modality of intra-arterial chemotherapy with caution and hope.
Pathophysiological consequences of hypertension in the cardiovascular system Longstanding hypertension

Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension.
The importance of adult couple relationships in primary care

Why should primary care practitioners be interested in the adult couple relationship, something that seems in-between the needs of individuals to have their care needs recognised and the needs of families to support parenting and protect and nurture healthy children? Aren’t couple relationships best seen as a matter for the partners involved, rather than as a focus for interventions? The short answer is that a focus on the adult couple relationship can be one of the most effective ways of supporting and helping individuals, parents, and children. There is now a considerable body of evidence that points to the fundamental importance of adult couple relationships for a variety of physical and mental health outcomes for both adults and children. The evidence comes from a variety of sources: randomized controlled studies of therapies for specific disorders; naturalistic studies of the impacts of clinics that offer help to couples (Hewison et al., 2016); and communitybased epidemiological surveys that look at correlations and prevalence. Much comes from the study of marriages and some from committed relationships, whether gay or straight, but all highlight the interdependency of good relationships and well-being.
Tumor Islands in Resected Early-stage Lung Adenocarcinomas are Associated With Unique Clinicopathologic and Molecular Characteristics and Worse Prognosis

Tumor islands—large collections of tumor cells isolated within alveolar spaces—can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and with the main tumor in different tissue planes, raising the possibility of tumor islands being a means of extension. However, the clinical and prognostic significance of tumor islands remains unknown. In this study, we compared clinicopathologic and molecular characteristics and prognosis of stages I to II lung adenocarcinomas with tumor islands (n=58) and those without (n=203). Lung adenocarcinomas with tumor islands were more likely to occur in smokers, exhibit higher nuclear grade and a solid or micropapillary pattern of growth, and harbor KRAS mutations. In contrast, lung adenocarcinomas without tumor islands were more likely to present as minimally invasive adenocarcinoma, show a lepidic pattern of growth, and harbor EGFR mutations. Although there was no difference in stage, the prognosis of lung adenocarcinomas with tumor islands was significantly worse than those without. The 5-year recurrence-free survival for patients with tumor islands and those without was 44.6% and 74.4%, respectively (log rank P=0.010). The survival difference remained significant (P <0.020) by multivariate analysis, and the presence of tumor islands was associated with almost 2-fold increase in the risk of recurrence. Even in the stage IA cohort, more than half of the patients with tumor islands experienced recurrence within 5 years. Thus, aggressive surveillance and/or further intervention may be indicated for patients whose tumors exhibit tumor islands.
Using Hashtags to Capture Fine Emotion Categories from Tweets

Detecting emotions in microblogs and social media posts has applications for industry, health, and security. Statistical, supervised automatic methods for emotion detection rely on text that is labeled for emotions, but such data are rare and available for only a handful of basic emotions. In this article, we show that emotion‐word hashtags are good manual labels of emotions in tweets. We also propose a method to generate a large lexicon of word–emotion associations from this emotion‐labeled tweet corpus. This is the first lexicon with real‐valued word–emotion association scores. We begin with experiments for six basic emotions and show that the hashtag annotations are consistent and match with the annotations of trained judges. We also show how the extracted tweet corpus and word–emotion associations can be used to improve emotion classification accuracy in a different nontweet domain.
Dynamic Enhancement of the Rat Inner Ear after Ultra-Small-Volume Administration of Gd-DOTA to the Medial Wall of the Middle Ear Cavity

Objective: To investigate minimally invasive administration of contrast agent to the middle ear and the enhancement efficacy on the inner ear compartments. Materials and Methods: An ultra-small volume of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA) was injected onto the medial wall of the rat middle ear with a high-performance polyimide tube. The dynamic Gd-DOTA distribution in the inner ear was visualized in vivo by MRI. Results: After injection of 2.5 µl of 0.5MGd-DOTA, uptake first occurred in the vestibulum, then in the scala vestibuli, and finally in the scala tympani (ST). A significant difference in signal intensities among these compartments was demonstrated with an intensity gradient, indicating that the vestibulum was the highest and the ST was the lowest. After 24 h, Gd-DOTA remained in the inner ear and the vestibule remained higher compared to the cochlea. The signal/noise ratio was significantly improved by a fluid-attenuated inversion recovery sequence. Conclusions: This novel minimally invasive technique can be applied to both animal studies and clinical evaluations of inner ear barrier function and fluid spaces with gadolinium-enhanced MRI. This technique might also be exploited for use as a minimally invasive drug delivery means for inner ear treatment.
Risk factors for prediction of inadequate response to antiresorptives

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross‐sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti‐osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual‐energy X‐ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47–8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55–9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93–0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem. © 2012 American Society for Bone and Mineral Research.
TP53 regulates miRNA association with AGO2 to remodel the miRNA–mRNA interaction network

DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage–induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA–mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2–miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis.
Added soft tissue contrast using signal attenuation and the fractal dimension for optical coherence tomography images of porcine arterial tissue

Optical coherence tomography (OCT) images of left-descending coronary tissues harvested from three porcine specimens were acquired with a home-build swept-source OCT setup. Despite the fact that OCT is capable of acquiring high resolution circumferential images of vessels, many distinct histological features of a vessel have comparable optical properties leading to poor contrast in OCT images. Two classification methods were tested in this report for the purpose of enhancing contrast between soft-tissue components of porcine coronary vessels. One method involved analyzing the attenuation of the OCT signal as a function of light penetration into the tissue. We demonstrated that by analyzing the signal attenuation in this manner we were able to differentiate two media sub-layers with different orientations of the smooth muscle cells. The other classification method used in our study was fractal analysis. Fractal analysis was implemented in a box-counting (fractal dimension) image-processing code and was used as a tool to differentiate and quantify variations in tissue texture at various locations in the OCT images. The calculated average fractal dimensions had different values in distinct regions of interest (ROI) within the imaged coronary samples. When compared to the results obtained by using the attenuation of the OCT signal, the method of fractal analysis demonstrated better classification potential for distinguishing amongst the tissue ROI.