Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic flexible versus rigid bronchoscopy for the assessment of tracheomalacia in children

Abstract Objective This project compares the degree of tracheal collapse determined by rigid and flexible bronchoscopy in paediatric patients with tracheomalacia. Methods A total of nine patients with tracheomalacia underwent both rigid and flexible video bronchoscopy. All patients were breathing spontaneously. Cross-sectional images of the airway were processed using the ImageJ program and analysed via colour histogram mode technique in order to delineate the luminal area. Paired t-tests (conducted using Stata software version 13.0) quantified differences between rigid and flexible bronchoscopes regarding the ratios of luminal pixels at maximum airway collapse to expansion. Correlation between both techniques in terms of airway collapse to expansion ratios was determined by calculating the Pearson correlation coefficient (R). Results The difference in ratios of maximum collapse to expansion between rigid and flexible bronchoscopy was not statistically significant (p = 0.4656) and was positively correlated (R = 0.523). Conclusion The ratios suggest that rigid and flexible bronchoscopy are equally efficacious in assessing tracheomalacia severity, and may be used interchangeably in a clinical setting.
Clear cell renal cell carcinoma with wild‐type von Hippel‐Lindau gene: a non‐existent or new tumour entity?

The current World Health Organisation (WHO) classification of renal tumours is based on characteristic histological features or specific molecular alterations. von Hippel‐Lindau (VHL) alteration is the hallmark of clear cell renal cell carcinoma (RCC). After identification of the MiT translocation family of tumours, clear cell papillary renal cancer and others, the group of ccRCC with wild‐type VHL is small. TCEB1 mutation combined with chromosome 8q loss is an emerging tumour entity with wild‐type VHL. Inactivation of TCEB1 increases HIF stabilisation via the same mechanism as VHL inactivation. Importantly, recent molecular analyses suggest the existence of another ‘VHL wild‐type’ evolutionary subtype of clear cell RCC in addition to TCEB1 mutated RCC and clear cell papillary renal cancer. These tumours are characterised by an aggressive behaviour, high tumour cell proliferation rate, elevated chromosomal instability and frequent presence of sarcomatoid differentiation. Future clinicopathological studies will have to provide data to determine whether TCEB1 tumours and clear cell RCC with wild‐type VHL are separate tumour entities or represent variants of a clear cell RCC tumour family.
[Staining effect of bovine incisors in vitro by tea solutions].

OBJECTIVE To determine the optimum staining condition of tea solutions on bovine incisors in vitro, by comparing the color stability of tooth surface of different concentrations of tea solutions and methods on bovine incisors in vitro. METHODS Twenty bovine incisors with color surface A1 were chosen, then randomly divided into 4 groups (n=10). Group 1: soaked with 2% tea solution continuously for 6 days; group 2: soaked with 2% tea solution for 6 days, but changed fresh tea solution everyday; group 3: soaked with 1% tea solution continuously for 6 days; group 4: soaked with 1% tea solution for 6 days but fresh tea solution changed every day. After 6 days of staining, the surface color (Δ E value) of all the samples were measured with crystal eye. After brushing 30 times with toothbrushes, the color of bovine incisors were measured again. Then the samples were soaked in artificial saliva at 37 ° C, and Δ E value was measured for 14 days. RESULTS After staining for 6 days, the Δ E values of the 2% tea solution groups were better than those of the 1% groups (20.21 vs. 16.44, 24.09 vs. 19.22, P<0.05); the groups with the same tea solution concentration, a better result was observed for the group soaked with daily fresh tea solution than for the group that experienced continuous staining (24.09 vs. 20.21, 19.22 vs. 16.44, P<0.05). Groups 1 and 2 were selected for subsequent brushing experiments. The color of both groups became lighter after brushing, and a better result was observed for the continuous staining group than for the group stained in daily fresh solution (3.06 vs. 9.51, P<0.05). The samples with better coloring effect soaked with 2% tea solution continuously for 6 days were put into artificial saliva for 14 days. There was not any significant change in coloring at the end of the first two days (1.51 vs. 1.51, P>0.05), and the color was visibly lighter after the third day (1.51 vs. 5.89, P<0.05), and no further significant change was observed until the 14th day (5.81 vs.5.89, P>0.05), which was darker coloring than that of the pre-staining group. CONCLUSION Continuous staining on bovine incisors with 2% tea solution with subsequent soaking in artificial saliva resulted in consistent coloring from day 3 to day 14, and this method could be used as an ideal model for teeth staining in vitro.
The Advantages and Disadvantages of Online and Blended Therapy: Survey Study Amongst Licensed Psychotherapists in Austria

Background Web-based and blended (face-to-face plus Web-based) interventions for mental health disorders are gaining significance. However, many licensed psychotherapists still have guarded attitudes toward computer-assisted therapy, hindering dissemination efforts. Objective The objective of this study was to provide a therapist-oriented evaluation of Web-based and blended therapies and identify commonalities and differences in attitudes toward both formats. Furthermore, it aimed to test the impact of an information clip on expressed attitudes. Methods In total, 95 Austrian psychotherapists were contacted and surveyed via their listed occupational email address. An 8-minute information video was shown to half of the therapists before 19 advantages and 13 disadvantages had to be rated on a 6-point Likert scale. Results The sample resembled all assessed properties of Austrian psychotherapists (age, theoretical orientation, and region). Therapists did not hold a uniform overall preference. Instead, perceived advantages of both interventions were rated as neutral (t94=1.89, P=.06; d=0.11), whereas Web-based interventions were associated with more disadvantages and risks (t94=9.86, P<.001; d=0.81). The information clip did not excerpt any detectable effect on therapists’ attitudes (r95=−.109, P=.30). The application of modern technologies in the own therapeutic practice and cognitive behavioral orientation were positively related to the given ratings. Conclusions This study is the first to directly compare therapists’ attitudes toward Web-based and blended therapies. Positive attitudes play a pivotal role in the dissemination of new technologies, but unexperienced therapists seem to lack knowledge on how to benefit from technology-aided treatments. To speed up implementation, these aspects need to be addressed in the development of new interventions. Furthermore, the preference of blended treatments over Web-based interventions seems to relate to avoidance of risks. Although this study is likely to represent therapists’ attitudes in countries with less advanced electronic health services, therapists’ attitudes in more advanced countries might present differently.
Association between cumulative methotrexate dose, non‐invasive scoring system and hepatic fibrosis detected by Fibroscan in rheumatoid arthritis patients receiving methotrexate

Methotrexate (MTX) is recommended by recent American College of Rheumatology and European League against Rheumatism guidelines as a first‐line drug for rheumatoid arthritis (RA). Liver fibrosis, which occurs as a long‐term side effect is of major concern. Monitoring aminotransferase and albumin is suggested in the guidelines, unfortunately this method is unreliable for detecting liver fibrosis. We try to find the association between clinical parameters, cumulative MTX dosage, liver fibrosis scoring systems and the presence of liver fibrosis assessed by transient elastography (TE; Fibroscan®).
The use of modern telemedicine technologies in an innovative optimal cardiac rehabilitation program for patients after myocardial revascularization: Concept and design of RESTORE, a randomized clinical trial

Despite proven efficacy of cardiac rehabilitation (CR) in reducing the all-cause mortality in patients after myocardial revascularization, the penetration of CR, due to patient-related factors and referral rates remains limited. To improve the outcomes, home-based tele-rehabilitation (TR) has been proposed recently. In theory TR enhances the effects of standard CR procedures due to implementation of an intelligent monitoring system designed to ensure optimal training through on-demand transmission of vital signs, aimed at motivating the patients through daily schedule reminders, setting daily goals and creating a platform for mutual feedback. Several meta-analyses assessing various studies comparing these two methods (CR and TR) have proven that they are at least equally effective, with some of the research showing superiority of TR. Although there was a small sample size, lack of long-term follow-up, reporting effects of TR itself, no integration with tools designed for coaching, motivating and promoting a healthy lifestyle constitutes an important limitation. The latter carries a hopeful prognosis for improvement when utilizing a broad-spectrum approach, especially with use of dedicated technological solutions exploiting the fact of a large and yet rapidly increasing penetration of smartphones, mobile PCs and tablets in the population. The above-mentioned findings worked as the basis and rationale for commencing the RESTORE project aimed at developing and delivering state-of-the-art, comprehensive TR for patients after myocardial revascularization and evaluating its molecular aspect in view of how it influences the atherosclerosis progression attenuation. This paper presents the current state and rationale behind the project based on up-to-date TR efficacy data.
Graphene Based Poly(Vinyl Alcohol) Nanocomposites Prepared by In Situ Green Reduction of Graphene Oxide by Ascorbic Acid: Influence of Graphene Content and Glycerol Plasticizer on Properties

The enhanced properties of polymer nanocomposites as compared with pure polymers are only achieved in the presence of well-dispersed nanofillers and strong interfacial adhesion. In this study, we report the preparation of nanocomposite films based on poly(vinyl alcohol) (PVA) filled with well dispersed graphene sheets (GS) by in situ reduction of graphene oxide (GO) dispersed in PVA solution using ascorbic acid (L-AA) as environmentally friendly reductant. The combined effect of GS content and glycerol as plasticizer on the structure, thermal, mechanical, water absorption, and water barrier properties of PVA/GS nanocomposite films is studied for the first time. Higher glass transition temperature, lower crystallinity, melting, and crystallization temperature, higher mechanical properties, and remarkable improvement in the thermal stability compared to neat PVA are obtained as a result of strong interfacial interactions between GS and PVA by hydrogen bonding. PVA/GS composite film prepared by ex situ process is more brittle than its in situ prepared counterpart. The presence of GS improves the water barrier and water resistance properties of nanocomposite films by decreasing water vapor permeability and water absorption of PVA. This work demonstrates that the tailoring of PVA/GS nanocomposite properties is enabled by controlling GS and glycerol content. The new developed materials, particularly those containing plasticizer, could be potential carriers for transdermal drug delivery.
Population pharmacokinetic modeling of flurbiprofen, the active metabolite of flurbiprofen axetil, in Chinese patients with postoperative pain

Background Flurbiprofen axetil, a lipid-microsphere-carrier targeting preparation, is a non-steroidal anti-inflammatory drug indicated for the treatment of postoperative pain. Aim The aim of the study was to develop a population pharmacokinetic (PPK) model of flurbiprofen, the active metabolite of flurbiprofen axetil, and optimize the treatment of flurbiprofen axetil in Chinese patients. Methods A total of 144 therapeutic drug-monitoring samples of flurbiprofen axetil from 72 patients were included in this study. The pharmacologically active metabolite flurbiprofen was used as the analytical target and determined 5–45 minutes after intravenous administration. The PPK model for flurbiprofen was developed using Phoenix NLME 1.3 with a nonlinear mixed-effect model. Bootstrap and visual predictive checks were used simultaneously to validate the final PPK model. Potential covariates of age, sex, body weight, height, and body-mass index were tested for PK parameters. Results The PPK model of flurbiprofen was explained by a one-compartment model with first-order elimination, in which a hypothetical-effect compartment was linked to a PK compartment. Population mean values of PK parameters estimated in the final model were θKe=0.0015/h, θVd=7.91 L, and θCL=1.55 L/h. Analysis of covariates showed that height and weight influenced the Ke of flurbiprofen. The final model was proved to be robust. Conclusion The final PPK model was demonstrated to be appropriate and effective, and can be used to assess the PK parameters of flurbiprofen in Chinese patients with postoperative pain.
Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants

Abstract Introduction: Extremely premature infants are susceptible to fluctuations in cerebral blood flow due to immaturity of cerebral autoregulation. Inotropes may cause rapid changes to systemic blood pressure and consequently cerebral blood flow, especially within the first 72 hours of life. This period is recognized to carry the greatest risk for cerebral hemorrhage. This study evaluates the incidence of death and/or severe brain injury in extremely preterm infants treated with inotropes in the first 72 hours of life. Methods: Prospective cohort study of infants born ≤29+0 weeks gestational age (GA) between January 2013 and December 2016. Severe brain injury was defined based on head ultrasound as presence of: grade III or IV intraventricular hemorrhage (IVH), moderate to severe post-hemorrhagic ventricular dilatation (PHVD), or cystic periventricular leukomalacia (cPVL). The association between inotrope use and death and/or brain injury was explored via logistic regression controlling for predefined confounding risk factors. Results: Of 497 eligible infants, 97 (19.5%) received inotropes during the first 72 hours. GA at birth, birth weight (BW), and 5-minute Apgar scores were lower among infants who received early inotropes compared to those not treated with inotropes. A stepwise logistic regression of the predefined confounding factors showed GA, exposure for antenatal steroids, and admission hypothermia to be significant confounding factors. Adjusting for those factors, early use of inotropes was associated with increased risk of death and/or severe brain injury (AOR 4.5; 95%CI: 2.4–8.5), severe brain injury (AOR 4.2; 95% CI: 1.9–8.9), and IVH of any grade (AOR 2.9; 95%CI: 1.7–4.9). Conclusion: Early inotropes use was associated with higher risk of death and/or severe brain injury. Strict indications and strategies for minimizing inotrope use while preventing hypotension should be implemented in the early postnatal care of infants at risk for severe brain injury.
Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases

Impaired muscle strength and mass (sarcopenia) are common in patients with respiratory cachexia, namely chronic obstructive pulmonary disease (COPD) and in lung cancer (LC)‐cachexia. Misfolded/unfolded proteins in endoplasmic reticulum (ER) induce the compensatory unfolded protein response (UPR). Expression of ER stress and UPR markers may be differentially upregulated in vastus lateralis (VL) of patients with respiratory sarcopenia associated with either a chronic condition (COPD) or subacute (LC)‐cachexia. In VL specimens from 40 COPD patients (n = 21, sarcopenic, fat‐free mass index [FFMI] 16 kg/m2 and n = 19, nonsarcopenic, FFMI 18 kg/m2), 13 patients with LC‐cachexia (FFMI 17 kg/m2), and 19 healthy controls (FFMI 19 kg/m 2), expression markers of ER stress, UPR (protein kinase‐like ER kinase [PERK], activating transcription factor [ATF] 6, and inositol‐requiring enzyme [IRE] 1‐α), oxidative stress, autophagy, proteolysis, and apoptosis (reverse transcription polymerase chain reaction and immunoblotting), and fiber atrophy (histology) were assessed. Atrophy and muscle wasting and weakness were seen in both groups of sarcopenic patients. Compared to healthy controls, in muscles of LC‐cachexia patients, expression of ER stress markers and UPR (three arms) was significantly upregulated, while in sarcopenic COPD, expression of a few ER stress markers and IRE1‐α arm was upregulated. ER stress and an exaggerated UPR were observed in the VL muscle of patients with respiratory sarcopenia. The three branches of UPR were similarly upregulated in muscles of cancer cachectic patients, whereas in sarcopenic COPD patients, only IRE1 was upregulated. The differential profile of muscle UPR in chronic and subacute respiratory conditions offers a niche for the design of specific novel therapeutic approaches.
Clinical significance of PD-1/PD-Ls gene amplification and overexpression in patients with hepatocellular carcinoma

Background: The remarkable clinical activity of PD-1 antibody in advanced hepatocellular carcinoma (HCC) highlights the importance of PD-1/PD-L1-mediated immune escape as therapeutic target in HCC. However, the frequency and prognostic significance of PD-Ls genetic alterations in HCC remain unknown. Methods: Fluorescence in situ hybridization were used to determine PD-Ls genetic alterations, and qPCR data coupled with immunofluorescence were used to measure the mRNA and protein levels of PD-Ls. Clinical relevance and prognostic value of 9p24.1 genetic alterations were investigated on tissue microarray containing three independent cohorts of 578 HCC patients. The results were further validated in an independent cohort of 442 HCC patients from The Cancer Genome Atlas (TCGA) database. Results: In total, 7.1%-15.0% for amplification and 15.8%-31.3% for polysomy of 9p24.1 were revealed in three cohorts of HCC patients, similar to the objective response rate of PD-1 antibody in HCC. Patients with 9p24.1 genetic alterations significantly and independently correlated with unfavorable outcomes than those without. FISH and qPCR data coupled with immunofluorescence revealed that genetic alterations of 9p24.1 robustly contributed to PD-L1 and PD-L2 upregulation. In addition, increased expression of PD-L1 instead of PD-L2 also predicted poor survival by multivariate analyses. Meanwhile, high infiltration of PD-1+ immune cells also indicated dismal survival in HCC. Conclusions: Amplification or higher expression of PD-L1 significantly and independently correlated with unfavorable survival in HCC patients, authenticating the PD-1/PD-L1 axis as rational immunotherapeutic targets for HCC.
How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 randomised controlled trials assessing exercise and medication effects on systolic blood pressure

Objective To compare the effect of exercise regimens and medications on systolic blood pressure (SBP). Data sources Medline (via PubMed) and the Cochrane Library. Eligibility criteria Randomised controlled trials (RCTs) of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-2 receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs) and diuretics were identified from existing Cochrane reviews. A previously published meta-analysis of exercise interventions was updated to identify recent RCTs that tested the SBP-lowering effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions (up to September 2018). Design Random-effects network meta-analysis. Outcome Difference in mean change from baseline SBP between comparator treatments (change from baseline in one group minus that in the other group) and its 95% credible interval (95% CrI), measured in mmHg. Results We included a total of 391 RCTs, 197 of which evaluated exercise interventions (10 461 participants) and 194 evaluated antihypertensive medications (29 281 participants). No RCTs compared directly exercise against medications. While all medication trials included hypertensive populations, only 56 exercise trials included hypertensive participants (≥140 mmHg), corresponding to 3508 individuals. In a 10% random sample, risk of bias was higher in exercise RCTs, primarily due to lack of blinding and incomplete outcome data. In analyses that combined all populations, antihypertensive medications achieved higher reductions in baseline SBP compared with exercise interventions (mean difference −3.96 mmHg, 95% CrI −5.02 to −2.91). Compared with control, all types of exercise (including combination of endurance and resistance) and all classes of antihypertensive medications were effective in lowering baseline SBP. Among hypertensive populations, there were no detectable differences in the SBP-lowering effects of ACE-I, ARB, β-blocker and diuretic medications when compared with endurance or dynamic resistance exercise. There was no detectable inconsistency between direct and indirect comparisons. Although there was evidence of small-study effects, this affected both medication and exercise trials. Conclusions The effect of exercise interventions on SBP remains under-studied, especially among hypertensive populations. Our findings confirm modest but consistent reductions in SBP in many studied exercise interventions across all populations but individuals receiving medications generally achieved greater reductions than those following structured exercise regimens. Assuming equally reliable estimates, the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications. Generalisability of these findings to real-world clinical settings should be further evaluated.
The Potential of South African Herbal Tisanes, Rooibos and Honeybush in the Management of Type 2 Diabetes Mellitus

Diabetes mellitus is a metabolic disease that can lead to high morbidity, mortality and long-term complications. Available treatment strategies, which are mainly based on treating hyperglycemia, with insulin and other pharmacological agents are not completely efficient and can even lead to development of unwanted side effects. Scientific evidence suggests that bioactive compounds from teas and other plant-based foods, which are known source of natural antioxidants, could be an attractive strategy to preferentially treat and manage type 2 diabetes mellitus (T2DM) and thus, have significant therapeutic implications. In this review, we attempt an in-depth analysis and discussion of the current progress in our understanding of the antidiabetic potential of two commercialized South Africa herbal tisanes—Rooibos and Honeybush and their polyphenols.