Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in baseline characteristics and 1-year psychological factors between participants and non-participants in the randomized, controlled trial regarding patient-led follow-up after rectal cancer (FURCA)

Abstract Background: The ongoing multi-center randomized FURCA-trial investigates the effect of patient-led follow-up after rectal cancer, aiming at improving management of late effects and survivorship care. The purpose of this present sub-study was to identify potential systematic differences between participants and non-participants in the FURCA-trial, in regard to demographic and clinical factors at baseline, and in quality of life (QoL) and fear of cancer recurrence (FCR) after one year. Material and methods: The population comprised patients invited to the FURCA-trial during the first 13 months’ recruitment. Clinical and demographic data was obtained at baseline and differences were significance tested. Non-participants were requested to fill in a short survey one year after primary surgery, while participants received the questionnaires as part of more comprehensive one-year follow-up. Results: In the first 13 months of the trial, 113 out of the 262 patients invited, declined to participate. The main reason reported for this was lack of energy surplus. Participants were younger than non-participants (p < .01), and nonparticipation was particularly evident among patients ≥ 80 years. More than half of the invited females declined to participate. Good WHO Performance status was associated with participation (p = .01), yet there were no statistically significant differences in Charlson Comorbidity Index, type of surgery, oncological treatment or UICC stages between participants and non-participants. By one year after surgery, there was no difference in FCR-level (p = .92) and QoL (p = .25) between the non-participants and control group participants. Conclusion: The sub-study found that participants and non-participants differed at baseline in regard to age, gender and performance status, which is supported by results from other studies. No between-group differences were found in psychological factors after one year. These findings are important for the generalisability of the upcoming results from the trial.
Brain natriuretic peptide reflects individual variation in hydration status in hemodialysis patients

Introduction: Fluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP.
Effects of HIV-1 gp120 and TAT-derived microvesicles on endothelial cell function.

The aims of this study were twofold. The first was to determine if human immunodeficiency virus (HIV)-1 glycoprotein (gp) 120 and transactivator of transcription (Tat) stimulate the release of endothelial microvesicles (EMVs). The second was to determine whether viral protein-induced EMVs are deleterious to endothelial cell function (inducing endothelial cell inflammation, oxidative stress, senescence and increasing apoptotic susceptibility). Human aortic endothelial cells (HAECs) were treated with recombinant HIV-1 proteins Bal gp120 (R5), Lav gp120 (X4), or Tat. EMVs released in response to each viral protein were isolated and quantified. Fresh HAECs were treated with EMVs generated under control conditions and from each of the viral protein conditions for 24 h. EMV release was higher (P < 0.05) in HAECs treated with R5 (141 ± 21 MV/µl), X4 (132 ± 20 MV/µl), and Tat (130 ± 20 MV/µl) compared with control (61 ± 13 MV/µl). Viral protein EMVs induced significantly higher endothelial cell release of proinflammatory cytokines and expression of cell adhesion molecules than control. Reactive oxygen species production was more pronounced (P < 0.05) in the R5-, X4- and Tat-EMV-treated cells. In addition, viral protein-stimulated EMVs significantly augmented endothelial cell senescence and apoptotic susceptibility. Concomitant with these functional changes, viral protein-stimulated EMVs disrupted cell expression of micro-RNAs 34a, 126, 146a, 181b, 221, and miR-Let-7a (P < 0.05). These results demonstrate that HIV-1 gp120 and Tat stimulate microvesicle release from endothelial cells, and these microvesicles confer pathological effects on endothelial cells by inducing inflammation, oxidative stress, and senescence as well as enhancing susceptibility to apoptosis. Viral protein-generated EMVs may contribute to the increased risk of vascular disease in patients with HIV-1. NEW & NOTEWORTHY Human immunodeficiency virus (HIV)-1-related proteins glycoprotein (gp) 120 and transactivator of transcription (Tat)-mediated endothelial damage and dysfunction are poorly understood. Endothelial microvesicles (EMVs) serve as indicators and potent mediators of endothelial dysfunction. In the present study we determined if HIV-1 R5- and X4-tropic gp120 and Tat stimulate EMV release in vitro and if viral protein-induced EMVs are deleterious to endothelial cell function. gp120 and Tat induced a marked increase in EMV release. Viral protein-induced EMVs significantly increased endothelial cell inflammation, oxidative stress, senescence, and apoptotic susceptibility in vitro. gp120- and Tat-derived EMVs promote a proinflammatory, pro-oxidative, prosenescent, and proapoptotic endothelial phenotype and may contribute to the endothelial damage and dysfunction associated with gp120 and Tat.
Cone beam CT imaging of the mandibular third molar: a position paper prepared by the European Academy of DentoMaxilloFacial Radiology (EADMFR).

OBJECTIVES Lack of evidence on the use of CBCT for management of mandibular third molars in Radiation Protection guideline no. 172 of the European Commission made the European Academy of DentoMaxilloFacial Radiology (EADMFR) decide to update the recommendations of the guideline. METHODS AND MATERIALS A literature search was performed addressing the following questions: (1) does CBCT change the treatment of the patient? ; (2) does CBCT reduce the number of post-operative sensory disturbances of the inferior alveolar nerve? ; and (3) can CBCT predict the risk for a post-operative sensory disturbance of the inferior alveolar nerve? RESULTS: Since the European Commission published the guideline in 2012 several high-evidence studies on the use of CBCT before removal of mandibular third molars have been conducted including five randomized controlled clinical trials and one meta-analysis. Present literature allows to propose recommendations with highest level of evidence. CONCLUSION New and up-to-date evidence-based recommendations advocate that CBCT imaging of the mandibular third molar should not be applied as a routine method before removal of mandibular third molars and therefore, CBCT imaging should only be applied when the surgeon has a very specific clinical question in an individual patient case that cannot be answered by conventional (panoramic and/or intraoral) imaging.
Outcomes of Anticoagulation Therapy in Adults With Tetralogy of Fallot

Background Available outcomes data for anticoagulation therapy in adults with congenital heart disease (CHD) provide assessment of global risk of this therapy for CHD patients (a heterogeneous population), but the risk of complications for the different CHD diagnoses is unknown. The purpose of the study was to describe the indications for anticoagulation, and the incidence and risk factors for major bleeding complication in adults with tetralogy of Fallot. Methods and Results We queried Mayo Adult Congenital Heart Disease (MACHD) database for tetralogy of Fallot patients (aged ≥18 years) that received anticoagulation, 1990–2017. Of 130 patients (42±14 years, 75 men [58%]), warfarin and direct oral anticoagulants were used in 125 (96%) and 5 (4%), respectively because atrial arrhythmias (n=109), mechanical prosthetic valve (n=29), intracardiac thrombus (n=4), pulmonary embolism (n=6), stroke (n=3), and perioperative anticoagulation (n=44). The median hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score for the entire cohort was 1 (0–2) and 27 (21%) had hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2. There were 14 minor bleeding events (1.6% per year) and 11 major bleeding events (1.3% per year) in 8 patients during median follow‐up of 74 months (856 patient‐years). Mechanical prosthesis (hazard ratio 1.78, CI 1.29–3.77, P=0.021) and hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2 (hazard ratio 1.41, CI 1.03–3.88, P=0.046) were risk factors for major bleeding events. All‐cause mortality was higher in patients with major bleeding events (n=6, 75%) compared with patients without major bleeding events (n=25, 21%), P=0.001. Conclusions Considering the heterogeneity of the CHD population, data from the current study may be better suited for clinical decision‐making in tetralogy of Fallot patients.
Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy.
Mechanisms of a locally adaptive shift in allocation among growth, reproduction, and herbivore resistance in Mimulus guttatus

Environmental gradients can drive adaptive evolutionary shifts in plant resource allocation among growth, reproduction, and herbivore resistance. However, few studies have attempted to connect these adaptations to the underlying physiological and genetic mechanisms. Here, we evaluate potential mechanisms underlying a coordinated locally adaptive shift between growth, reproduction, and herbivore defense in the yellow monkeyflower, Mimulus guttatus. Through manipulative laboratory experiments we found that gibberellin (GA) growth hormones may play a role in the developmental divergence between coastal perennial and inland annual ecotypes of M. guttatus. Further, we detected an interaction between a locally adaptive chromosomal inversion, DIV1, and GA addition. This finding is consistent with the inversion contributing to the evolution of growth form via an interaction with the GA pathway. Finally, we found evidence that the DIV1 inversion is partially responsible for a coordinated shift in the divergence of growth, reproduction, and herbivore resistance traits between coastal perennial and inland annual M. guttatus. The inversion has already been established to have a substantial impact on the life-history shift between long-term growth and rapid reproduction in this system. Here, we demonstrate that the DIV1 inversion also has sizable impacts on both the total abundance and profile of phytochemical compounds involved in herbivore resistance.
Epitope-Specific Serological Assays for RSV: Conformation Matters

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in children and older adults. An effective vaccine must elicit neutralizing antibodies targeting the RSV fusion (F) protein, which exists in two major conformations, pre-fusion (pre-F) and post-fusion (post-F). Although 50% of the surface is shared, pre-F contains highly neutralization-sensitive antigenic sites not present on post-F. Recent advancement of several subunit F-based vaccine trials has spurred interest in quantifying and understanding the protective potential of antibodies directed to individual antigenic sites. Monoclonal antibody competition ELISAs are being used to measure these endpoints, but the impact of F conformation and competition from antibodies binding to adjacent antigenic sites has not been thoroughly investigated. Since this information is critical for interpreting clinical trial outcomes and defining serological correlates of protection, we optimized assays to evaluate D25-competing antibodies (DCA) to antigenic site Ø on pre-F, and compared readouts of palivizumab-competing antibodies (PCA) to site II on both pre-F and post-F. We show that antibodies to adjacent antigenic sites can contribute to DCA and PCA readouts, and that cross-competition from non-targeted sites is especially confounding when PCA is measured using a post-F substrate. While measuring DCA and PCA levels may be useful to delineate the role of antibodies targeting the apex and side of the F protein, respectively, the assay limitations and caveats should be considered when conducting immune monitoring during vaccine trials and defining correlates of protection.
Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1-like subgroup characterized by high non-response and relapse rates

Outcome in adult precursor B-cell acute lymphoblastic leukemia (BCP-ALL) is unsatisfactory, with complete response rates of approximately 80% and event-free survival at 5 years of only 40%–50%. [1][1] This inferior survival in adult compared with pediatric patients might be explained by a higher
Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis

Objective To investigate the effect of menarche, pregnancies, and breastfeeding on the risk of developing multiple sclerosis (MS) and disability accrual using a multivariate approach based on a large prospective cohort of patients with clinically isolated syndrome (CIS). Methods A cross-sectional survey of the reproductive information of female participants in a CIS cohort was performed. We examined the relationship of age at menarche with the risk of clinically definite MS (CDMS), McDonald 2010 MS, and Expanded Disability Status Scale (EDSS) 3.0 and 6.0. The effect of pregnancy (before and after CIS) and breastfeeding in the risk of CDMS, McDonald 2010 MS, and EDSS 3.0 was also examined. Univariate and multivariate analyses were performed and findings were confirmed using sensitivity analyses and a propensity score model. Results The data of 501 female participants were collected. Age at menarche did not correlate with age at CIS and was not associated with the risk of CDMS or EDSS 3.0 or 6.0. Pregnancy before CIS was protective for CDMS in the univariate analysis, but the effect was lost in the multivariate model and did not modify the risk of EDSS 3.0. Pregnancy after CIS was protective for both outcomes in univariate and multivariate analyses when pregnancy was considered a baseline variable, but the protective effect disappeared when analyzed as a time-dependent event. Breastfeeding did not modify the risk for the 3 outcomes. Conclusions These results demonstrate that menarche, pregnancies, and breastfeeding did not substantially modify the risk of CDMS or disability accrual using a multivariable and time-dependent approach.
Social Media Based Analysis of Opioid Epidemic Using Reddit

Opioid-abuse epidemic in the United States has escalated to national attention due to the dramatic increase of opioid overdose deaths. Analyzing opioid-related social media has the potential to reveal patterns of opioid abuse at a national scale, understand opinions of the public, and provide insights to support prevention and treatment. Reddit is a community based social media with more reliable content curated by the community through voting. In this study, we collected and analyzed all opioid related discussions from January 2014 to October 2017, which contains 51,537 posts by 16,162 unique users. We analyzed the data to understand the psychological categories of the posts, and performed topic modeling to reveal the major topics of interest. We also characterized the extent of social support received from comments and scores by each post. Last, we analyzed statistically significant difference in the posts between anonymous and non-anonymous users.
Epigenetics and genomics in Turner syndrome

The pathogenesis of Turner syndrome (TS) and the genotype–phenotype relationship has been thoroughly investigated during the last decade. It has become evident that the phenotype seen in TS does not only depend on simple gene dosage as a result of X chromosome monosomy. The origin of TS specific comorbidities such as infertility, cardiac malformations, bone dysgenesis, and autoimmune diseases may depend on a complex relationship between genes as well as transcriptional and epigenetic factors affecting gene expression across the genome. Furthermore, two individuals with TS with the exact same karyotype may exhibit completely different traits, suggesting that no conventional genotype–phenotype relationship exists. Here, we review the different genetic mechanisms behind differential gene expression, and highlight potential key‐genes essential to the comorbidities seen in TS and other X chromosome aneuploidy syndromes. KDM6A, important for germ cell development, has shown to be differentially expressed and methylated in Turner and Klinefelter syndrome across studies. Furthermore, TIMP1/TIMP3 genes seem to affect the prevalence of bicuspid aortic valve. KDM5C could play a role in the neurocognitive development of Turner and Klinefelter syndrome. However, further research is needed to elucidate the genetic mechanism behind the phenotypic variability and the different phenotypic traits seen in TS.
Screening for lymphangioleiomyomatosis by high-resolution computed tomography in young, nonsmoking women presenting with spontaneous pneumothorax is cost-effective.

RATIONALE Women with pulmonary lymphangioleiomyomatosis (LAM) who present with a sentinel spontaneous pneumothorax (SPTX) will experience an average of 2.5 additional pneumothoraces. The diagnosis of LAM is typically delayed until after the second pneumothorax. OBJECTIVES We hypothesized that targeted screening of an LAM-enriched population of nonsmoking women between the ages of 25 and 54 years, who present with a sentinel pneumothorax indicated by high-resolution computed tomography (HRCT), will facilitate early identification, definitive therapy, and improved quality of life for patients with LAM. METHODS We constructed a Markov state-transition model to assess the cost-effectiveness of screening. Rates of SPTX and prevalence of LAM in populations stratified by age, sex, and smoking status were derived from the literature. Costs of testing and treatment were extracted from 2007 Medicare data. We compared a strategy based on HRCT screening followed by pleurodesis for patients with LAM, versus no HRCT screening. MEASUREMENTS AND MAIN RESULTS The prevalence of LAM in nonsmoking women, between the ages of 25 and 54 years, with SPTX is estimated at 5% on the basis of the available literature. In our base case analysis, screening for LAM by HRCT is the most cost-effective strategy, with a marginal cost-effectiveness ratio of $32,980 per quality-adjusted life-year gained. Sensitivity analysis showed that HRCT screening remains cost-effective for groups in which the prevalence of LAM in the population subset screened is greater than 2.5%. CONCLUSIONS Screening for LAM by HRCT in nonsmoking women age 25-54 that present with SPTX is cost-effective. Physicians are advised to screen for LAM by HRCT in this population.
Relationship Between Contact Lens and Pinguecula.

PURPOSE To investigate the effects of contact lens (CL) on the frequency of pinguecula, and the relationship between dry eye disease and pinguecula. METHODS Two hundred and 33 cases of soft CL wearers and 230 age-matched nonwearers were enrolled in the study. Schirmer I test (ST) scores and tear break-up time (TBUT) were determined in all participants. A questionnaire including ocular surface disease index (OSDI), age, sex, and duration of CL wear was implemented to the participants before the examination. RESULTS The prevalence of pinguecula was 27.8% (n: 65) in the CL group and 26.5% (n: 61) in the control group. There was no significant difference between the groups (P=0.841). The prevalence of pinguecula increased with age in both groups. There was no significant difference in the prevalence of pinguecula when users were divided into three groups according to the duration of CL wear (P=0.575). The TBUT scores were lower, and the OSDI scores were higher in the CL group. The TBUT scores were lower in patients with pinguecula in both groups. The OSDI scores were higher in the CL group. There was no significant difference regarding the OSDI scores between patients with pinguecula and healthy participants in the CL group; however, OSDI scores were significantly higher in patients with pinguecula in control group. There were no significant differences in the ST scores between the groups, and between patients with pinguecula and healthy participants. CONCLUSION This is the second study that evaluates the effects of soft CL wearing on pinguecula prevalence. We found that CL wearing does not affect the prevalence of pinguecula. Considering the OSDI scores in patients with pinguecula in the CL group, CL may suppress the irritant symptoms of pinguecula.