Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine learning-based unenhanced CT texture analysis for predicting BAP1 mutation status of clear cell renal cell carcinomas

Background BRCA1-associated protein 1 (BAP1) mutation is an unfavorable factor for overall survival in patients with clear cell renal cell carcinoma (ccRCC). Radiomics literature about BAP1 mutation lacks papers that consider the reliability of texture features in their workflow. Purpose Using texture features with a high inter-observer agreement, we aimed to develop and internally validate a machine learning-based radiomic model for predicting the BAP1 mutation status of ccRCCs. Material and Methods For this retrospective study, 65 ccRCCs were included from a public database. Texture features were extracted from unenhanced computed tomography (CT) images, using two-dimensional manual segmentation. Dimension reduction was done in three steps: (i) inter-observer agreement analysis; (ii) collinearity analysis; and (iii) feature selection. The machine learning classifier was random forest. The model was validated using 10-fold nested cross-validation. The reference standard was the BAP1 mutation status. Results Out of 744 features, 468 had an excellent inter-observer agreement. After the collinearity analysis, the number of features decreased to 17. Finally, the wrapper-based algorithm selected six features. Using selected features, the random forest correctly classified 84.6% of the labelled slices regarding BAP1 mutation status with an area under the receiver operating characteristic curve of 0.897. For predicting ccRCCs with BAP1 mutation, the sensitivity, specificity, and precision were 90.4%, 78.8%, and 81%, respectively. For predicting ccRCCs without BAP1 mutation, the sensitivity, specificity, and precision were 78.8%, 90.4%, and 89.1%, respectively. Conclusion Machine learning-based unenhanced CT texture analysis might be a potential method for predicting the BAP1 mutation status of ccRCCs.
Polyfluorene-Based Multicolor Fluorescent Nanoparticles Activated by Temperature for Bioimaging and Drug Delivery

Multifunctional nanoparticles have been attracting growing attention in recent years because of their capability to integrate materials with different features in one entity, which leads them to be considered as the next generation of nanomedicine. In this work, we have taken advantage of the interesting properties of conjugated polyelectrolytes to develop multicolor fluorescent nanoparticles with integrating imaging and therapeutic functionalities. With this end, thermosensitive liposomes were coated with three recently synthesized polyfluorenes: copoly-((9,9-bis(6′-N,N,N-trimethylammonium)hexyl)-2,7-(fluorene)-alt-1,4-(phenylene)) bromide (HTMA-PFP), copoly-((9,9-bis(6′-N,N,N-trimethylammonium)hexyl)-2,7-(fluorene)-alt-4,7-(2- (phenyl)benzo(d) (1,2,3) triazole)) bromide (HTMA-PFBT) and copoly-((9,9-bis(6′-N,N,N- trimethylammonium)hexyl)-2,7-(fluorene)-alt-1,4-(naphtho(2,3c)-1,2,5-thiadiazole)) bromide (HTMA-PFNT), in order to obtain blue, green and red fluorescent drug carriers, respectively. The stability, size and morphology of the nanoparticles, as well as their thermotropic behavior and photophysical properties, have been characterized by Dynamic Light Scattering (DLS), Zeta Potential, transmission electron microscope (TEM) analysis and fluorescence spectroscopy. In addition, the suitability of the nanostructures to carry and release their contents when triggered by hyperthermia has been explored by using carboxyfluorescein as a hydrophilic drug model. Finally, preliminary experiments with mammalian cells demonstrate the capability of the nanoparticles to mark and visualize cells with different colors, evidencing their potential use for imaging and therapeutic applications.
Salivary Gland FNA Diagnostics in a Real-Life Setting: One-Year-Experiences of the Implementation of the Milan System in a Tertiary Care Center

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 following other organ specific cytopathological reporting systems and it aimed at bringing a practical, evidence-based, user-friendly classification system with characterization and management algorithms. At the Department of Pathology, Fimlab Laboratories, Tampere, Finland all salivary fine needle aspirations (FNAs) have been given cytopathological diagnoses according to the MSRSGC since January 2018. Analyses of a one-year-period (January 2018–December 2018) consisted of 183 salivary FNA samples from 138 patients with correlation to histopathology in 90 cases with surgical follow-up. The MSRSGC performance in patient based analysis was as follows: accuracy was 90.9%, sensitivity was 61.5%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 89.4%, respectively. Risks of malignancy (ROMs) in MSRSGC categories were: 0.0% (0/15) in non-diagnostic category, 100.0% (1/1) in non-neoplastic category biased by only one falsely-negative lymphoma case, 14.3% (1/7) in atypia of undetermined significance category, 0.0% (0/28) in benign neoplasm category, 27.3% (3/11) in neoplasm of uncertain malignant potential category, and 100% for both suspicious for malignancy (4/4) and malignancy (4/4) categories, respectively. The MSRSGC has been proven as a reliable classification system in salivary gland FNA routine diagnostics in a tertiary care center.
Social Environment and Individual Differences in Feeding Behavior Are Associated with Risk of Endometritis in Dairy Cows

Simple Summary The aim of this study was to determine how individual differences in behavior affect disease risk in Holstein dairy cows housed in two different social environments: (1) a predictable and non-competitive social environment and (2) an unpredictable and competitive social environment. Individual differences in feed intake and feeding behavior before calving were associated with cytological endometritis post-calving; however, the direction and magnitude of these effects were dependent on the social environment. These results provide the first evidence that individual differences in feeding behavior affect cytological endometritis risk differently depending on the social environment. Abstract Our aim was to determine whether individual differences in feeding and social behavior in different social environments affect health outcomes in dairy cows. We used eight groups of four animals per treatment assigned to either a ‘predictable’ or an ‘unpredictable’ and competitive social environment. Predictable cows were given free access to six feed bins with no change in feed delivery times; whereas, the unpredictable cows were required to share one feed bin with one resident cow and morning feed was delayed 0, 1, 2, or 3 h every other day. On alternate days, the unpredictable cows were also re-assigned to a new bin and a new resident partner. Low daily dry matter intake (DMI) was a risk factor for cytological endometritis in predictable cows (odds ratio (OR) (95% confidence interval): 0.17 (0.02, 0.53)), but low daily DMI was protective for unpredictable cows (OR: 1.93 (1.09, 4.14)). Although low rate of DMI (kg/min) was a risk factor for cytological endometritis for predictable cows (OR: 4.2 × 10−101 (8.6 × 10−206, 4.8 × 10−30)) it was unrelated to disease for unpredictable cows. There were no associations between feed bin visits or percentage of non-nutritive visits with the likelihood of cytological endometritis. This is the first evidence that individual differences in feeding behavior influence cytological endometritis risk in dairy cows, but the direction and magnitude of these effects is dependent on the social environment.
Total corneal refractive power and shape in Down syndrome

Purpose: To determine the total corneal refractive power in 1–8 mm corneal zones and the 8 mm Q-value in non-keratoconic patients with Down syndrome and normal subjects aged 10–30 years. Methods: Right eye data from 203 Down syndrome patients (mean ± standard deviation age: 17.0 ± 4.7 years) and 189 age- and gender-matched normal subjects (17.1 ± 4.5 years) were compared. Main extracted Pentacam indices were total corneal refractive power in steep and flat axes, and mean and difference (corneal astigmatism) total corneal refractive power in 1–8 mm zones. Results: Mean total corneal refractive power in 1–8 mm zones was 45.17–45.74 D and 42.91–43.52 D in Down and normal group, respectively (all p < 0.001). The coefficients of variation of total corneal refractive power from the center to the periphery were similar in the two groups (p = 0.855). None of the mean total corneal refractive powers significantly correlated with age, and all of them were significantly higher in females (p < 0.001). Mean total corneal refractive power–based corneal astigmatism in these zones changed from 1.46 to 1.66 D in Down syndrome patients and 1.64 to 1.99 D in normal group. All corneal astigmatism indices were similar between two groups (all p > 0.05). The prevalence of against the rule and oblique astigmatism in all zones were higher in the Down syndrome group (all p < 0.05). Conclusion: Adolescent and young non-keratoconic patients with Down syndrome have a more prolate cornea and a homogeneous keratometry distribution. In this population, females have a steeper cornea.
A unique flipped classroom approach shows promising results in physician assistant education

Abstract Aims: The flipped classroom (FC) model utilizes pre-class foundational learning with in-class higher-order application exercises. FC approaches have reported positive perceptions and mixed academic performance outcomes in medical education; however, little evidence exists on their impact in the 56-week didactic curriculum of Physician Assistant (PA) education. Methods: A 4-week FC curriculum was piloted in a PA behavioral medicine course (n = 34). Before class, students completed online video modules. During class, students completed a pre-class quiz and answered clinical case-based questions in a think-pair-share format. Results: Students rated in-class time higher than a lecture-based segment of the same course (p = 0.028). Assessment of achievement emotions demonstrated increased enjoyment (p = 0.028) and decreased boredom (p < 0.001) in the FC curriculum with no difference in anxiety. The FC curriculum produced a 57.2 min increase in pre-class preparation time with no change in post-class studying time. Compared to historical lecture-based controls (n = 35), students in the FC curriculum scored significantly higher on clinical vignette questions (p = 0.019) with equivalent performance on other question formats. Conclusions: This study offers the first positive outcomes of an FC approach in PA education and provides a framework for improving academic performance while scaling back in-class time.
Comparison between Ozurdex and intravitreal anti-vascular endothelial growth factor treatment for retinal vein occlusion–related macular edema: A systematic review and meta-analysis of randomized controlled trials

This systematic review aimed to evaluate the effectiveness and safety of intravitreal dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatments for macular edema (ME) secondary to retinal vein occlusion (RVO), central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO). The electronic databases comprehensively searched for the studies that compared DEX with anti-VEGF treatments in patients suffering from RVO-related ME. The effectiveness was estimated using best-corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP). All data were analyzed by Review Manager (RevMan) 5.3. According to the meta-analysis from five randomized control trials, both DEX implant and anti-VEGF agent treatments were effective, but no significant differences in BCVA and CRT were observed between these two treatments. Novartis' two studies indicated that anti-VEGF agents significantly reduced the CRT compared with DEX implant at 6 months [weighted mean difference: 158.53 μm, 95% confidence interval (CI): (71.09, 245.96), P= 0.0004]. Furthermore, anti-VEGF agents showed some advantages on cataract formation [risk ratio (RR): 3.43, 95% CI: (1.35, 8.71), P= 0.009] and other adverse events [RR: 1.19, 95% CI: (1.09, 1.31), P= 0.0002] without heterogeneity (P = 0.20, I2 = 35%). Anti-VEGF agents were also effective treatments for cataract formation or less adverse events for RVO-related ME. In contrast, DEX implant had higher risk for IOP elevation and lower cataract incidence than anti-VEGF agents. Hence, complementary and alternative treatments are expected.
Early-stage 11C-Flumazenil PET predicts day-14 selective neuronal loss in a rodent model of transient focal cerebral ischemia

Predicting tissue outcome early after stroke is an important goal. MRI >3 h accurately predicts infarction but is insensitive to selective neuronal loss (SNL). Previous studies suggest that chronic-stage 11 C-flumazenil PET (FMZ-PET) is a validated marker of SNL in rats, while early-stage FMZ-PET may predict infarction. Whether early FMZ-PET also predicts SNL is unknown. Following 45-min distal MCA occlusion, adult rats underwent FMZ-PET at 1 h and 48 h post-reperfusion to map distribution volume (VT), which reflects GABA-A receptor binding. NeuN immunohistochemistry was performed at Day 14. In each rat, VT and %NeuN loss were determined in 44 ROIs spanning the hemisphere. NeuN revealed isolated SNL and cortical infarction in five and one rats, respectively. In the SNL subgroup, VT-1 h was mildly reduced and only weakly predicted SNL, while VT-48 h was significantly increased and predicted SNL both individually (p < 0.01, Kendall) and across the group (p < 0.001), i.e. the higher the VT, the stronger the SNL. Similar correlations were found in the rat with infarction. Our findings suggest GABA-A receptors are still present on injured neurons at the 48 h timepoint, and the increased 48 h VT observed here is consistent with earlier rat studies showing early GABA-A receptor upregulation. That FMZ binding at 48 h was predictive of SNL may have clinical implications.
Interaction of a Polyarginine Peptide with Membranes of Different Mechanical Properties

The membrane translocation efficiency of cell penetrating peptides (CPPs) has been largely studied, and poly-arginines have been highlighted as particularly active CPPs, especially upon negatively charged membranes. Here we inquire about the influence of membrane mechanical properties in poly-arginine adsorption, penetration and translocation, as well as the subsequent effect on the host membrane. For this, we selected anionic membranes exhibiting different rigidity and fluidity, and exposed them to the nona-arginine KR9C. Three different membrane compositions were investigated, all of them having 50% of the anionic lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DOPG), thus, ensuring a high affinity of the peptide for membrane surfaces. The remaining 50% was a saturated PC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC), an unsaturated PC (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) or a mixture of DOPC with cholesterol. Peptide-membrane interactions were studied using four complementary models for membranes: Langmuir monolayers, Large Unilamellar Vesicles, Black Lipid Membranes and Giant Unilamellar Vesicles. The patterns of interaction of KR9C varied within the different membrane compositions. The peptide strongly adsorbed on membranes with cholesterol, but did not incorporate or translocate them. KR9C stabilized phase segregation in DPPC/DOPG films and promoted vesicle rupture. DOPC/DOPG appeared like the better host for peptide translocation: KR9C adsorbed, inserted and translocated these membranes without breaking them, despite softening was observed.
Fat Graft Enhanced With Adipose-Derived Stem Cells in Aesthetic Breast Augmentation: Clinical, Histological, and Instrumental Evaluation.

BACKGROUND Fat graft enhanced with adipose-derived stem cells (FG-e-ASCs) has been utilized in outcomes of radiotherapy after mastectomy, breast soft tissue defects, ulcers, and loss of substance. The authors present their experience using FG-e-ASCs in breast augmentation. OBJECTIVES The aim of this study was to evaluate the safety and efficacy of a study group (SG) regarding the use of FG-e-ASCs in breast augmentation for aesthetic improvement, comparing the results with a control group (CG). METHODS A total of 46 patients affected by breast hypoplasia were treated with FG-e-ASCs, comparing results with those of a CG (n = 30) treated with fat graft not enhanced with adipose-derived stem cells (FG-ne-ASCs). The preoperative evaluation included a complete clinical evaluation, a photographic assessment, magnetic resonance imaging (MRI) of the soft tissue, ultrasound (US), and mammography (MG). Postoperative follow-up took place at 1, 3, 7, 12, 24, and 48 weeks, and then annually. RESULTS The patients treated with FG-e-ASCs showed 58% maintenance of the contour restoring and of 3-dimensional (3D) volume after 3 years compared with the patients of the CG treated with FG-ne-ASCs, who showed 29% maintenance. In 67.4% (n = 31) of breast augmentation treated with FG-e-ASCs, we observed a restoration of the breast contour and an increase of 10.3 mm in the 3D volume after 36 months, which was observed in only 20.0% (n = 6) of patients in the CG treated with FG-ne-ASCs. Volumetric persistence in the SG was higher than that in the CG (P < .0001 SG vs. CG). CONCLUSIONS The use of FG-e-ASCs was safe and effective in this series of cases performed.
Health Inequality Among the Elderly in Rural China and Influencing Factors: Evidence from the Chinese Longitudinal Healthy Longevity Survey

Based on data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), this paper calculates the health distribution of the elderly using the Quality of Well-Being Scale (QWB) score, and then estimates health inequality among the elderly in rural China using the Wagstaff index (WI) and Erreygers index (EI). Following this, it compares health inequalities among the elderly in different age groups, and finally, uses the Shapley and recentered influence function-index-ordinary least squares (RIF-I-OLS) model to decompose the effect of four factors on health inequality among the elderly in rural China. The QWB score distribution shows that the health of the elderly in rural China improved with social economic development and medical reform from 2002 to 2014. However, at the same time, we were surprised to find that the health level of the 65–74 years old group has been declining steadily since 2008. This phenomenon implies that the incidence of chronic diseases is moving towards the younger elderly. The WI and EI show that there is indeed pro-rich health inequality among the rural elderly, the health inequality of the younger age groups is more serious than that of the older age groups, and the former incidence of health inequality is higher. Health inequality in the age group of 65–74 years old is higher than that in other groups, and the trend of change fluctuated downward from 2002 to 2014. Health inequality in the age group of 75–84 years old is lower than that in the group of 65–74 years old, but higher than that in the other age groups. The results of Shapley decomposition show that demographic characteristics, socioeconomic status (SES), health care access, and quality of later life contributed 0.0054, 0.0130, 0.0442, and 0.0218 to the health inequality index of the elderly, which accounted for 6.40%, 15.39%, 52.41%, and 25.80% of health inequality index. From the results of RIF-I-OLS decomposition, this paper has analyzed detailed factors’ marginal effects on health inequality from four dimensions, which indicates that the health inequality among the elderly in rural China was mainly caused by the disparity of income, medical expenses, and living arrangement.
Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients

Augmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates were studied in static-concentration time-kill studies. One isolate was examined comprehensively in a 7-day hollow-fiber infection model (HFIM). ABSTRACT Augmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates were studied in static-concentration time-kill studies. One isolate was examined comprehensively in a 7-day hollow-fiber infection model (HFIM). Pharmacokinetic profiles representing substantial ARC (creatinine clearance of 250 ml/min) were generated in the HFIM for meropenem (1 g or 2 g administered every 8 h as 30-min infusion and 3 g/day or 6 g/day as continuous infusion [CI]) and tobramycin (7 mg/kg of body weight every 24 h as 30-min infusion) regimens. The time courses of total and less-susceptible bacterial populations and MICs were determined for the monotherapies and all four combination regimens. Mechanism-based mathematical modeling (MBM) was performed. In the HFIM, maximum bacterial killing with any meropenem monotherapy was ∼3 log10 CFU/ml at 7 h, followed by rapid regrowth with increases in resistant populations by 24 h (meropenem MIC of up to 128 mg/liter). Tobramycin monotherapy produced extensive initial killing (∼7 log10 at 4 h) with rapid regrowth by 24 h, including substantial increases in resistant populations (tobramycin MIC of 32 mg/liter). Combination regimens containing meropenem administered intermittently or as a 3-g/day CI suppressed regrowth for ∼1 to 3 days, with rapid regrowth of resistant bacteria. Only a 6-g/day CI of meropenem combined with tobramycin suppressed regrowth and resistance over 7 days. MBM described bacterial killing and regrowth for all regimens well. The mode of meropenem administration was critical for the combination to be maximally effective against carbapenem-resistant P. aeruginosa.
IMPACT OF ADMISSION NON STRESS TEST AS A SCREENING PROCEDURE ON PERINATAL OUTCOME

Objectives: To evaluate the role of admission non stress test as a screening method in low and high risk pregnancies and to assess the perinatal outcome. Methods: In this study 326 women with singleton term pregnancies admitted in established labour were subjected to admission stress test (AST). These women were classified into three subgroups according to result of AST: Reactive, Equivocal and Non reactive group. Perinatal outcome was evaluated in all the groups along with sensitivity, specificity, positive and negative predictive values of the test. Results: caesarean and instrumental delivery rates for fetal distress were higher in non-reactive and equivocal group than in the reactive group. Perinatal morbidity in reactive, equivocal and non reactive groups was 4.8%, 28.94% and 55.92% respectively. Sensitivity and specificity of the test in this study were 63.63% and 93.33% respectively. Positive predictive value was 55.26%, while negative predictive value was 95.2%. Conclusion: Admission stress test can be used as a primary screening technique to pick up high risk fetuses and thus timely intervention can reduce perinatal morbidity.