Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperbranched Cationic Glycogen Derivative-Mediated IκBα Gene Silencing Regulates the Uveoscleral Outflow Pathway in Rats

The role of the IκB/NF-κB signaling pathway in the uveoscleral outflow pathway was investigated with IκBα gene silencing mediated by the 3-(dimethylamino)-1-propylamine-conjugated glycogen (DMAPA-Glyp) derivative. The IκBα-siRNA-loaded DMAPA-Glyp complex was transfected into the ciliary muscles of rats by intracameral injection (labeled as the DMAPA-Glyp+siRNA group). The Lipofectamine™ 2000 (Lipo)/siRNA complex and the naked siRNA were set as the controls. The mRNA and protein expression of IκBα, NF-κBp65, and MMP-2 were analyzed by real-time PCR, western blotting, and in situ gelatin zymography. Nuclear translocation of NF-κBp65 was analyzed by immunofluorescence. Rat intraocular pressure (IOP) was monitored pre- and postinjection. Gene transfection efficiency and toxicity of the DMAPA-Glyp derivative were also evaluated. After RNA interference (RNAi), IκBα mRNA and protein expression were significantly inhibited. NF-κBp65 mRNA and protein expression showed no significant differences. Nevertheless, nuclear translocation of NF-κBp65 occurred in the DMAPA-Glyp+siRNA group. Both mRNA expression and activity of MMP-2 increased, with the largest increase in the DMAPA-Glyp+siRNA group. IOP in the DMAPA-Glyp+siRNA group fell to the lowest level on day 3 after RNAi. The levels of Cy3-siRNA in the ciliary muscle of the DMAPA-Glyp+siRNA group did not significantly decrease over time. At 7 and 14 d after RNAi, no significant pathological damage was detectable in the eyes injected with the DMAPA-Glyp derivative or the DMAPA-Glyp/siRNA complex. Taken together, our results suggest that downregulation of IκBα expression in the ciliary muscle plays a crucial role in reducing the IOP values of rats. IκBα may become a new molecular target for lowering IOP in glaucoma. The DMAPA-Glyp derivative is safe and feasible as an effective siRNA vector in rat eyes.
Choroidal Thickness Evaluation in a Transfusion-Dependent Beta-Thalassemia Greek Population

Purpose To evaluate choroidal thickness in a group of beta-thalassemia patients as assessed by enhanced depth imaging optical coherence tomography. Patients and Methods This single-center, observational study involved transfusion-dependent beta-thalassemia (TD-β-thal) patients and healthy controls. One eye of each participant was included in the study. Submacular and peripapillary choroidal thickness, as well as central macular thickness and retinal nerve fiber layer thickness, were evaluated. Results Thirty-eight TD-β-thal patients (mean age 42 ± 10.7 years) and 22 healthy controls (mean age 40.3 ± 10.2 years) were included in the study. Subfoveal choroidal thickness was 297.4 ± 74.5 μm in the patient group and 358.4 ± 71.4 μm in the control group (p=0.003). Overall, in the submacular area, the choroid was found to be significantly thinner in the beta-thalassemia population compared to controls in all evaluated points, except for the spot located 1500 μm nasally to the fovea (p=0.093). In the peripapillary area, choroidal thickness was also significantly lower in the thalassemic population compared to the controls (nasal p=0.033, temporal p=0.01, superior p=0.01), except for the inferior quadrant (p= 0.191). We did not observe statistically significant differences in the retinal nerve fiber layer thickness and the central macular thickness between the two groups (p=0.658 and p=0.276, respectively). No correlations with hemoglobin, serum ferritin or iron levels emerged. Patients with the intermediate subtype appeared to have significantly thinner choroids than the ones with thalassemia major. Conclusion Our findings suggest that choroidal thickness in the submacular and peripapillary area is significantly reduced in thalassemic patients, compared to healthy individuals. Choroidal thinning in beta-thalassemia possibly reflects the effect of chronic anemia and underlying hemodynamic changes on choroidal tissue.
Cutaneous Metastasis as the First Presentation of Non-Small-Cell Lung Cancer with a BRAF Mutation: A Case Report

Abstract Cutaneous metastasis from a primary visceral malignancy is a relatively uncommon clinical manifestation that occurs as an initial presentation in 1% to 12% of patients with internal malignancies. Additionally, cutaneous metastases are often late signs of an internal malignancy, and in very rare cases they may occur at the same time or before the primary cancer has been detected. Metastasis to the skin has a poor prognosis and is often a sign of widespread malignant tumors. In the present study, we report a 72-year-old male who presented with multiple rapidly growing subcutaneous nodules. Positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic concentration of radiotracer in the left lower lung and multiple organ metastases associated with multiple skin masses. Biopsy of one of the skin nodules and gene detection indicated metastatic adenocarcinoma consistent with a primary lung origin with a BRAF mutation. BRAF mutations are emerging therapeutic targets in non-small-cell lung cancer (NSCLC), as they are present in 2–4% of NSCLC cases. To the best of our knowledge, this is the first case report to show that BRAF-mutant lung adenocarcinoma can be associated with cutaneous metastasis. Early diagnosis and individualized treatment strategies may prolong patient survival.
Treatment Outcomes and Associated Factors among Children Hospitalized with Acute Bacterial Meningitis in Eastern Ethiopia: A Cross-Sectional Study

Background Bacterial meningitis is a common central nervous system infection that is associated with high morbidity and mortality in pediatrics. In Ethiopia, little is known about treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children. Objective To assess treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children with acute bacterial meningitis in the Hiwot Fana Specialized University Hospital pediatric ward. Methods A retrospective cross-sectional study was conducted at the pediatric ward of Hiwot Fana Specialized University Hospital, eastern Ethiopia. Relevant data were collected using a structured data-collection tool from patients’ medical charts. Bivariate and multivariate logistic regression analyses were done to identify predictors of treatment outcomes. OR with 95% CI and P≤0.05 was used for statistical significance. Results A total of 200 children with acute bacterial meningitis were included in the study, of which 92% were aged ≥2 months and the majority (128, 64%) had delayed (≥72 hours) presentation to the hospital. At admission, 181 (90.5%) were febrile, 92 (46%) had depressed level of consciousness, and 40 (20%) had had seizures. Most (126, 63%) had documented medical comorbidities. The antibiotic combination of ampicillin and gentamycin had been frequently administered in children aged <2 months while ceftriaxone was commonly prescribed for those aged >2 months. Of the total study participants, 154 (77%) showed successful treatment outcomes, while 46 (23%) experienced poor treatment outcomes (died or “self”-discharged). Level of consciousness (AOR 3.25, 95% CI 1.21–8.75), duration of illness before admission (AOR 3.74, 95% CI 1.76–7.98), and antibiotic-regimen change (AOR 4.7, 95% CI 2.4–10) were predictors of treatment outcomes. Conclusion The majority of study participants experienced good treatment outcomes. Unconsciousness, antibiotic-regimen change, and duration of illness before hospitalization were significantly associated with treatment outcomes. Early treatment, linkage of primary-health facilities to tertiary health–care centers, and availability of diagnostics should be promoted to improve patient outcomes.
Expression of Toll-Like Receptors in the Animal Model of Bladder Outlet Obstruction

Introduction Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. Material and Methods. Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP—sham-operated rats with a placebo (water); SOB—sham-operated rats with an alpha-1 adrenergic antagonist; BOOP—rats with BOO and a placebo; and BOOB—rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study. Results Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18). Conclusions The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.
Forensic Validity of the Third Molar Maturity Index (I3M) for Age Estimation in a Russian Population

The aim of this cross-sectional study was to test the accuracy of the third molar maturity index (I3M) cut-off value (0.08) to distinguish between individuals above and below the adult age of legal responsibility (18 years) in a Russian population. A sample of 571 digital panoramic radiographs of healthy Russian minors and young adults (363 females and 208 males), aged between 14 and 24 years, was evaluated. The lower left third molars were analyzed by applying the cut-off value of 0.08 determined by Cameriere et al. (2008). Lin's concordance correlation coefficient (ρc) and Cohen's kappa coefficient (κ) showed that repeatability and reproducibility are high for both intra- and interobserver errors. The I3M value decreased with age in both sexes. Age distribution gradually decreases as I3M increases in both girls and boys. In the male group, molar maturity stages 0-0.04, 0.04-0.08, 0.08-0.3, 0.3-0.5, and 0.9-1.4 were reached slightly earlier than in the female group. The results demonstrated that sensitivity is 0.96 in boys and 0.93 in girls; associated specificity values were both 0.98. The cut-off value of I3M is statistically robust and thus valid for forensic application in a Russian population to determine whether or not a subject has reached 18 years of age. Finally, we compared our results with those of other studies in which the same I3M cut-off value was tested on different populations. The method is novel as it is reliable and easily reproducible, thus ensuring a universal way of comparing the results obtained (based on a cut-off value) among many populations, in order to develop an ever-increasing database.
Effects of Clinicopathological Characteristics on the Survival of Patients Treated with PD-1/PD-L1 Inhibitor Monotherapy or Combination Therapy for Advanced Cancer: A Systemic Review and Meta-Analysis

Background PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer. Methods A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed. Results Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 (P < 0.001) and 0.64 (P < 0.001), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54), and the difference was statistically significant (interaction, P = 0.005). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001) compared with male (HR, 0.73; P < 0.001; interaction, P = 0.004). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001) than smokers (HR, 0.63; P = 0.001; interaction, P = 0.02). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy. Conclusions Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.
Evaluation of articles in metabolism research on the basis of their citations

Introduction The number of research papers and journals each year is increasing and millions of dollars are spent. Despite this there is evidence to suggest that many publications do not impact clinical practice. We used citation analysis to measure the influence of metabolism publications from 2003-2013. Those papers with lower citation rates are likely to be of the least value and high rates of such publications may be a marker of research waste. Materials and methods We analysed 67 journals with 81,954 articles related to metabolism indexed on the Scopus station database from 2003-2013. We identified those articles with less than 5 citations within 5 years from publication date as poorly cited. Journals were ranked by the percentage of articles that were poorly cited or uncited. Results Over the 10-year period, the number of total articles increased by 127%. We found that 24% of articles were poorly cited within 5 years of publication. Journals in the bottom 25% and top 25% of rankings by citation rates accounted for a similar proportion of poorly cited articles. Most of the open access journals were ranked in the top 25% for citation rates. Conclusions Our analysis contradicts concerns over increasing amounts of publications with little impact. The proportion of poorly cited articles are low, with little change in the trend over 10 years. The top and bottom ranked journals produced similar proportions of poorly cited articles. These findings suggest the necessity of pursuing further research to study waste in metabolism research.
FDG PET Predicts the Effects of 131I and Prognosis for Patients with Bone Metastases from Differentiated Thyroid Carcinoma

Background 18F-FDG PET and 131I scans are important in the detection of metastases from differentiated thyroid carcinoma (DTC). The relationship of FDG and radioiodine (RAI) metabolism in bone metastases (BMs) from DTC and its prognostic value on RAI treatment is not clear. Methods The retrospective study included DTC patients with BMs from two medical centers, who underwent 18F-FDG PET/CT scans and RAI therapy. Therapeutic response was evaluated by serum thyroglobulin (Tg) levels and anatomical imaging changes. Results The analyses were performed on 30 patients with 72 BMs. Forty-two (42/72, 58%) lesions displayed simultaneous 131I and 18F-FDG uptake. BMs with positive 18F-FDG uptake had a less favorable response to RAI therapy in comparison to those with negative 18F-FDG uptake (p = 0.018), even in 131I-avid lesions (p = 0.033). Sixteen (53%) patients had disease progression with a median PFI of 26 months (range: 3 to 89 months). Compared to those with 131I-avid but non-FDG-avid BMs, patients presenting with 18F-FDG-avid BMs had shorter PFI, whether with 131I uptake (p = 0.002) or without (p = 0.002). Conclusion More than half of BMs (58%) from DTC show simultaneous 18F-FDG and 131I uptakes which are contrary to the flip-flop phenomenon (131I negative and 18F-FDG positive). Regardless of 131I uptake, 18F-FDG uptake of BMs portends a less favorable therapeutic response and poorer prognosis for patients with DTC.
Associations Between Service Members' Posttraumatic Stress Disorder Symptoms and Partner Accommodation Over Time.

When service members manifest symptoms of posttraumatic stress disorder (PTSD), intimate partners may engage in behaviors to accommodate their partners' experiences (e.g., helping service members avoid situations that could make them uncomfortable, not expressing own thoughts and feelings to minimize PTSD-related conflict), which may inadvertently serve to maintain or increase PTSD symptoms over time. In a sample of 274 male service member/female civilian couples, we evaluated hypothesized bidirectional pathways between self-reported service member PTSD symptoms and partner accommodation, assessed four times over an approximately 18-month period. A random-intercept cross-lagged panel model disaggregating between and within effects revealed that, on average, couples in which the service member had higher levels of total PTSD symptoms also scored higher in partner accommodation, between-couple correlation, r = . 40. In addition, at time points when service members' PTSD symptoms were higher relative to their own average symptom level, their partners' level of accommodation was also higher than their personal average, within-couple correlation r = . 22. Longitudinally, service member PTSD symptom scores higher than their personal average predicted subsequent increases in partner accommodation, β = . 19, but not vice versa, β = . 03. Overall, the findings indicate both stable and time-specific significant associations between service member PTSD symptoms and partner accommodation and suggest that higher levels of PTSD symptoms are a significant driver of later increases in partner accommodation. These findings add further support for treating PTSD in an interpersonal context to address the disorder and concomitant relational processes that can adversely impact individual and relational well-being.
Revisiting silica based ordered mesoporous materials: medical applications

The bioactivity behaviour of SBA-15, MCM-48, MCM-41 mesoporous materials, is revisited in this paper. The influence of their different textural and structural properties on apatite formation is outlined and strategies to modify their kinetics are proven and discussed. On the basis of the experimental data showing the feasibility of control of the bioactivity kinetics on mesoporous materials, together with their controlled drug release abilities, new possibilities for tissue engineering developments are proposed.
A Systematic Review of Scientific Studies on the Effects of Music in People with or at Risk for Eating Disorders.

BACKGROUND The prevalence of the three main eating disorders (EDs) anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) is increasing, and a growing number of patients with EDs is seeking professional help. Thus, there is a need for additional treatment strategies in EDs. The aim of this review was to summarize the literature on the benefits and risks of music as well as the evidence for its therapeutic application in people with EDs. METHODS Following the PRISMA guidelines, we performed a systematic literature review on scientific studies on the effect of music in people with or at risk for EDs using PubMed and the Web of Science database. The search terms used were: "music", "music therapy", "eating disorders", "anorexia nervosa", "bulimia nervosa" and "binge eating disorder". RESULTS 16 out of 119 identified and screened articles qualified as scientific studies involving a total of 3,792 participants. They reported on the use of music or music therapy in individuals with or at risk of AN and BN, but not BED. In inpatients with AN, listening to classical music was beneficial to food consumption. Singing in a group reduced post-prandial anxiety in AN inpatients and outpatients. Vodcasts which also included positive visual or autobiographical stimuli helped BN patients with anxiety and body image perception. Songwriting and sessions with a Body Monochord helped with the processing of therapeutically relevant topics in AN. Watching music videos, however, reinforced body dissatisfaction, drive for thinness, bodyweight concerns, preoccupation with physical appearance in pre-teenage and teenage girls, and drive for muscularity in adolescent boys. CONCLUSIONS These findings suggest that the therapeutic application of music may be beneficial in patients with AN and BN. However, the availability of studies with a rigorous randomized controlled trial (RCT) design is scarce.
Occupational exposures and exacerbations of asthma and COPD—A general population study

Purpose Recent studies suggest that occupational inhalant exposures trigger exacerbations of asthma and chronic obstructive pulmonary disease, but findings are conflicting. Methods We included 7,768 individuals with self-reported asthma (n = 3,215) and/or spirometric airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced expiratory volume (FVC) <0.70) (n = 5,275) who participated in The Copenhagen City Heart Study or The Copenhagen General Population Study from 2001–2016. Occupational exposure was assigned by linking job codes with job exposure matrices, and exacerbations were defined by register data on oral corticosteroid treatment, emergency care unit assessment or hospital admission. Associations between occupational inhalant exposure each year of follow-up and exacerbation were assessed by Cox regression with time varying exposure and age as the underlying time scale. Results Participants were followed for a median of 4.6 years (interquartile range, IQR 5.4), during which 870 exacerbations occurred. Exacerbations were not associated with any of the selected exposures (high molecular weight sensitizers, low molecular weight sensitizers, irritants or low and high levels of mineral dust, biological dust, gases & fumes or the composite variable vapours, gases, dusts or fumes). Hazards ratios ranged from 0.8 (95% confidence interval: 0.7;1.0) to 1.2 (95% confidence interval: 0.9;1.7). Conclusion Exacerbations of obstructive airway disease were not associated with occupational inhalant exposures assigned by a job exposure matrix. Further studies with alternative exposure assessment are warranted.