Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Mirabegron on Anxiety and Depression in Female Patients with Overactive Bladder

Background: Treatment of overactive bladder (OAB) with antimuscarinic agents has been shown to improve depression and/or anxiety symptoms. Objectives: The aim of this study was to evaluate the efficacy of mirabegron on OAB symptoms and its effects on depression and/or anxiety of treatment-naïve women with OAB. Methods: Women treated with mirabegron were prospectively evaluated by the OAB symptom score and hospital anxiety and depression Scale before and at 4 and 8 weeks after treatment. Wilcoxon signed-rank and Spearman rank correlation coefficient were used for statistical analyses, and a p value of < 0.05 was considered as significant. Results: Of the 112 patients who were enrolled, 25.0% had been previously diagnosed as having clinical anxiety and 22.3% as having clinical depression. The OAB, anxiety, and depression symptom scores were significantly improved at both 4 and 8 weeks (p < 0.05). Anxiety, but not depression, symptoms were significantly correlated with OAB symptoms. Conclusion: Improvement of OAB symptoms helps relieve anxiety, but not depression.
Diffusion-Weighted MRI for Lymphoma Staging—Letter

We read with interest the recent article by Mayerhoefer and colleagues ([1][1]). Their prospective study aimed to determine the diagnostic value of diffusion-weighted MRI (DWI-MRI), a potential radiation-free alternative to FDG-PET/CT, for pretreatment staging in 140 patients with various lymphoma
Neural cue reactivity during acute abstinence predicts short‐term smoking relapse

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence‐related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24‐hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short‐term (7‐day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7‐day relapse. The secondary smoking cessation outcome measure was total number of self‐reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole‐brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR = 2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P = 0.036). Greater abstinence‐induced change in ACC activation also predicted fewer total days abstinent (β = −0.63, 95% CI = 0.43 to 0.66, P < 0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.
Cerebrospinal fluids from Alzheimer's disease patients exhibit neurotoxic effects on neuronal cell cultures

A growing number of studies suggest amyloid‐β and tau present in cerebrospinal fluid (CSF) and blood as putative biomarkers for Alzheimer's disease (AD). However, there is a question whether these compounds present in patients’ bodily fluids can directly cause neurotoxic effects. We investigated effects of AD and other dementia (OD) patients’ blood serum and CSF on viability of cells in primary cerebellar granule cell cultures. Overall, 59 individuals participated in the study from whom 55 samples of biological fluids were taken. Participants were classified into early (E‐AD) and middle (M‐AD) stages of AD, cognitively healthy control (HC) and OD groups. We found that concentrations of total and phosphorylated tau were higher in CSF from AD patients, while amyloid‐β42 and amyloid‐β40 in the serum was lower compared to HC. The most cytotoxic effects were induced by CSFs from M‐AD patients which caused neuronal necrosis and suppressed microglial proliferation, whereas CSFs from the groups of other patients did not kill neurons. Serum and CSF from the E‐AD group caused a reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between the AD groups although both tau species in CSFs from M‐AD patients were found to be significantly elevated compared to HC. Our data suggest that biological fluids from E‐AD induce neuronal loss, whereas effects of CSF on the reduction in neuronal viability can serve as an indicator of M‐AD and may be associated with extracellular tau.
Platelet-Rich Fibrin Extract: A Promising Fetal Bovine Serum Alternative in Explant Cultures of Human Periosteal Sheets for Regenerative Therapy

In 2004, we developed autologous periosteal sheets for the treatment of periodontal bone defects. This regenerative therapy has successfully regenerated periodontal bone and augmented alveolar ridge for implant placement. However, the necessity for 6-week culture is a limitation. Here, we examined the applicability of a human platelet-rich fibrin extract (PRFext) as an alternative to fetal bovine serum (FBS) for the explant culture of periosteal sheets in a novel culture medium (MSC-PCM) originally developed for maintaining mesenchymal stem cells. Small periosteum tissue segments were expanded in MSC-PCM + 2% PRFext for 4 weeks, and the resulting periosteal sheets were compared with those prepared by the conventional method using Medium199 + 10% FBS for their growth rate, cell multilayer formation, alkaline phosphatase (ALP) activity, and surface antigen expression (CD73, CD90, and CD105). Periosteal sheets grew faster in the novel culture medium than in the conventional medium. However, assessment of cell shape and ALP activity revealed that the periosteal cells growing in the novel medium were relatively immature. These findings suggest that the novel culture medium featuring PRFext offers advantages by shortening the culture period and excluding possible risks associated with xeno-factors without negatively altering the activity of periosteal sheets.
Helpful strategies for GPs seeing patients with medically unexplained physical symptoms: a focus group study.

BACKGROUND Patients with long-lasting and disabling medically unexplained physical symptoms (MUPS) are common in general practice. GPs have previously described the challenges regarding management and treatment of patients with MUPS. AIM To explore GPs' experiences of the strategies perceived as helpful when seeing patients with MUPS. DESIGN AND SETTING Three focus group interviews with a purposive sample of 24 experienced GPs were held in southern Norway. METHOD Discussions were audiotaped and transcribed. Systematic text condensation was used for analysis. RESULTS Several strategies were considered helpful during consultations with patients with MUPS. A comprehensive outline of the patient's medical past and present could serve as the foundation of the dialogue. Reviewing the patient's records and sharing relevant information with them or conducting a thorough clinical examination could offer 'golden moments' of trust and common understanding. A very concrete exchange of symptoms and diagnosis interpretation sometimes created a space for explanations and action, and confrontations could even strengthen the alliance between the GP and the patient. Bypassing conventional answers and transcending tensions by negotiating innovative explanations could help patients resolve symptoms and establish innovative understanding. CONCLUSION GPs use tangible, down-to-earth strategies in consultations with patients with MUPS. Important strategies were: thorough investigation of the patient's symptoms and story; sharing of interpretations; and negotiation of different explanations. Sharing helpful strategies with colleagues in a field in which frustration and dissatisfaction are not uncommon can encourage GPs to develop sustainable responsibility and innovative solutions.
Comparison of 30-Day MACE between Immediate versus Staged Complete Revascularization in Acute Myocardial Infarction with Multivessel Disease, and the Effect of Coronary Lesion Complexity

Background and objective: In patients with acute myocardial infarction and multivessel disease, the timing of intervention to non-culprit lesions is still a matter of debate, especially in patients without shock. This study aimed to compare the effect of multivessel intervention, performed at index percutaneous coronary intervention (PCI) (MVI-I) or index hospitalization (MVI-S), on the 30-day results of acute myocardial infarction (AMI), and to investigate the effect of coronary lesion complexity assessed by the Syntax (Sx) score on the timing of multivessel intervention. Materials and methods: We enrolled 180 patients with MVI-I, and 425 patients with MVI-S. The major adverse cardiovascular events (MACE) for this study were identified as mortality, nonfatal myocardial infarction, nonfatal stroke, acute heart failure, ischemia driven revascularization, major bleeding, and acute renal failure developed within 30 days. Results: The unadjusted MACE rates at 30 days were 11.2% and 5% among those who underwent MVI-I and MVI-S, respectively (OR 3.02; 95% confidence interval (CI) 1.51–6.02; p = 0.002). Associations were statistically significant after adjusting for covariates in the penalized multivariable model (adjusted OR 2.06; 95%CI 1.02–4.18; p = 0.043), propensity score adjusted multivariable model (adjusted OR 2.46; 95%CI 1.19–5.07; p = 0.015), and IPW (adjusted OR 2.11; 95%CI 1.28–3.47; p = 0.041). We found that the Syntax score of lesions did not affect the results. Conclusion: MVI-S was associated with a lower incidence of major adverse cardiovascular events within 30 days after discharge.
Chromothripsis after Stumbling through DNA Replication

Most structural genome variations (SVs), such as chromosome translocations and inversions, are readily detected by classical chromosome banding in combination with molecular cytogenetic techniques. With steadily improving levels of resolution, the frequency of detection of SVs increases. At nucleotide resolution, these techniques will also allow us to investigate the sequences of the break points of the SVs and eventually their possible mechanism of origin. Using FISH, array CGH, Southern blot hybridization and MLPA, the break points of SVs were mapped, which then allowed us to determine the sequences surrounding the fusion points of these breaks [Higgins et al., 2008; Sobreira et al., 2011; Chiang et al., 2012]. Only one out of 17 fusions was perfectly balanced at the nucleiotide level [Higgins et al., 2008]. The overwhelming majority, roughly three quarters, involved insertions, deletions and stretches of microhomology of a few base pairs (bp), which is consistent with nonhomologous end joining (NHEJ). The remainder may have resulted from microhomology-mediated break-induced replication (MMBIR), since they involved more extensive DNA synthesis [Higgins et al., 2008; Sobreira et al., 2011; Chiang et al., 2012]. In a study of 8 de novo unbalanced translocations, which most likely occurred postzygotically, 5 indicated nonallelic homologous recombination between paralogous repeats as the predominant mechanism [Robberecht et al., 2013]. Apparently, at least 3 distinct pathways of ‘repair’ of chromosome breaks exist.
First-Line Nivolumab Plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers

PURPOSE CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non–small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB). PATIENTS AND METHODS Two hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point. RESULTS Of treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR increased with higher TMB, plateauing at 10 or more mutations/megabase (mut/Mb). Regardless of PD-L1 expression, ORRs were higher in patients with TMB of 10 or more mut/Mb (n = 48: PD-L1, ≥ 1%, 48%; PD-L1, < 1%, 47%) versus TMB of fewer than 10 mut/Mb (n = 50: PD-L1, ≥ 1%, 18%; PD-L1, < 1%, 5%), and progression-free survival was longer in patients with TMB of 10 or more mut/Mb versus TMB of fewer than 10 mut/Mb (median, 7.1 v 2.6 months). Grade 3 to 4 treatment-related adverse events occurred in 29% of patients. CONCLUSION Nivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab.
Intracoronary Eptifibatide Bolus Administration During Percutaneous Coronary Revascularization for Acute Coronary Syndromes With Evaluation of Platelet Glycoprotein IIb/IIIa Receptor Occupancy and Platelet Function: The Intracoronary Eptifibatide (ICE) Trial

Background— Eptifibatide reduces major adverse cardiac events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Intracoronary bolus administration of eptifibatide may result in higher levels of platelet glycoprotein IIb/IIIa receptor occupancy in the local coronary bed, disaggregate thrombus in the epicardial artery and microvasculature, and thereby improve coronary flow. Methods and Results— Patients undergoing PCI for an acute coronary syndrome were randomized to either intracoronary or intravenous bolus administration of eptifibatide. The primary end point was the local glycoprotein IIb/IIIa receptor occupancy measured in the coronary sinus. There were no angiographic, electrophysiological, or other adverse findings attributable to intracoronary eptifibatide. Platelet glycoprotein IIb/IIIa receptor occupancy was significantly greater with intracoronary versus intravenous administration: first bolus, 94±9% versus 51±15% (P<0.001); and second bolus, 99±2% versus 91±4% (P=0.001), respectively. Microvascular perfusion was significantly improved as measured by the corrected thrombolysis in myocardial infarction frame count (cTFC) with intracoronary versus intravenous administration: pre-PCI, 36 (median) (25th and 75th percentiles, 16 and 64) versus 31 (25th and 75th percentiles, 23 and 45; P=0.8); and post-PCI, 18 (25th and 75th percentiles, 10 and 22) versus 25 (25th and 75th percentiles, 22 and 35; P=0.007), respectively. The only multivariate predictor associated with a post-PCI cTFC rank score was the first bolus glycoprotein IIb/IIIa receptor occupancy (P<0.001). Conclusions— Intracoronary bolus administration of eptifibatide during PCI in patients with acute coronary syndromes results in higher local platelet glycoprotein IIb/IIIa receptor occupancy, which is associated with improved microvascular perfusion demonstrated by an improved cTFC.
Neutrophil Gelatinase‐Associated Lipocalin for Assessment of Acute Kidney Injury in Cirrhosis: A Prospective Study

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS‐AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase–associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin‐18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia‐induced AKI (48%), 93 were HRS‐AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78‐0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28‐day mortality together with Model for End‐Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.
Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Florfenicol, a structural analog of thiamphenicol, has broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic-pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK-PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time-killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr , AUC0-∞ , Tmax , T1/2 , Cmax , CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr-1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr-1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.
Reinfection by HCV following effective all-oral DAA therapy in HIV/HCV-coinfected individuals.

OBJECTIVES We analyzed HCV reinfection among participants in a prospective registry of HIV/HCV-coinfected patients treated with all-oral DAA-based therapy in the region of Madrid. DESIGN Observational cohort study. METHODS The study period started on the date SVR was confirmed. The censoring date was December 31, 2017. SVR was defined as negative HCV-RNA 12 weeks after completion of treatment. Reinfection was defined as a positive HCV-RNA test result after achievement of SVR. RESULTS Reinfections were detected in 17 of 2,359 HIV/HCV-coinfected patients (0.72%) overall, in 12 of 177 (6.78%) men who have sex with men MSM, and in 5 of 1,459 (0.34%) people who inject drugs (PWID). The incidence of reinfection (95% CI) per 100 person-years was 0.48 (0.30-0.77) overall, 5.93 (3.37-10.44) for MSM, and 0.21 (0.09-0.52) for PWID. Reinfections were detected a median of 14.86 weeks (IQR 13.43-25.71) after SVR. In 10 (58.82%) patients, the reinfection was caused by a different HCV genotype. All 12 MSM with reinfection acknowledged unprotected anal intercourse with several partners, 7 used chemsex, 6 reported fisting, and 4 practiced slamming. A concomitant STI was detected in 5 patients. Four IDU with reinfection reported injecting drugs following SVR. CONCLUSIONS HCV reinfection is a matter of concern in HIV-positive MSM treated with all-oral DAA therapy in the region of Madrid. Our data suggest that prevention strategies and frequent testing with HCV-RNA should be applied following SVR in MSM who engage in high-risk practices.
Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV.

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of β-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann-Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventy-six participants were included (128 HIV+ and 48 HIV-); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.