Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of two correlated ROC surfaces at a given pair of true classification rates

The receiver operating characteristic (ROC) curve is typically employed when one wants to evaluate the discriminatory capability of a continuous or ordinal biomarker in the case where two groups are to be distinguished, commonly the “healthy” and the “diseased. ” There are cases for which the disease status has three categories. Such cases employ the ROC surface, which is a natural generalization of the ROC curve for three classes. In this paper, we explore new methodologies for comparing two continuous biomarkers that refer to a trichotomous disease status, when both markers are applied to the same patients. Comparisons based on the volume under the surface have been proposed before, but that measure is often not clinically relevant. Here, we focus on comparing two correlated ROC surfaces at given pairs of true classification rates, which are more relevant to patients and physicians. We propose delta‐based parametric techniques, power transformations to normality, and bootstrap‐based smooth nonparametric techniques to investigate the performance of an appropriate test. We evaluate our approaches through an extensive simulation study and apply them to a real dataset from prostate cancer screening.
Evaluation of the anatomical measurements of the temporomandibular joint by cone-beam computed tomography.

BACKGROUND To examine the detailed anatomy of the normal temporomandibular joint (TMJ) in a large series of patients divided into different age groups. MATERIALS AND METHODS Cone-beam computed tomography images of 100 patients included in the study. Morphometric analysis regarding mandibular con- dyle and mandibular fossa, articular tubercle and the zygomatic arch was done. The volumetric and surface measurements of mandibular condyles (total tissue volume [TV], total bone volume [BV], bone surface area [BS] and percentage of bony tissue of the mandibular condyle [BV/TV]) were also measured. RESULTS Statistical analysis was performed and statistically significant differences according to the side of the joint, sex, and age groups were reported. Additionally, correlations between aging and all of these parameters were also determined. CONCLUSIONS TV, BV, BS and BV/TV parameters according to side, age, and sex groups were defined for normal TMJ which may help to understand the onset and progress of TMJ disorders.
A randomised controlled trial comparing adductor canal block and femoral nerve block for knee arthroplasty.

INTRODUCTION Adductor canal block (ACB) is hypothesised to provide superior analgesia to femoral nerve block (FNB) for total knee arthroplasty (TKA) while preserving quadriceps strength. METHODS 30 patients undergoing TKA were randomised to receive either ACB or FNB. Baseline tests of quadriceps strength were performed. Ultrasound-guided blocks with 30 mL of 0.5% ropivacaine were administered before induction of general anaesthesia. Patient-controlled analgesia (morphine) was prescribed for postoperative analgesia. The primary outcome of this prospective, double-blinded, randomised controlled trial was morphine consumption (mean ± standard deviation) in the first 24 hours. Secondary outcomes were pain scores using a numeric rating scale (median and interquartile range [IQR]), quadriceps strength (% of baseline) and functional outcomes at 24 hours and 48 hours postoperatively. RESULTS There was no statistically significant difference in morphine consumption at 24 hours between the ACB and FNB groups (21 ± 11 mg vs. 20 ± 12 mg; p = 0.85). No statistically significant differences were observed between the ACB and FNB groups in pain scores at 24 hours (at rest: 0 [IQR 0-2] vs. 0 [IQR 0-2]; on movement: 5 [IQR 4-8] vs. 5 [IQR 3-8]) and quadriceps strength (24 hours: 28.8% ± 26.1% vs. 26.8% ± 19.6% of baseline; 48 hours: 31.5 ± 23.1% vs. 33.7% ± 20.1% of baseline). There were also no statistically significant differences in functional outcomes and length of stay. CONCLUSION We found no statistically significant differences in analgesic effects, quadriceps strength or functional recovery postoperatively between ACB and FNB.
Sleep restriction during peripuberty unbalances sexual hormones and testicular cytokines in rats†

Abstract Spermatogenesis and steroidogenesis are not fully established during puberty. Especially during this period, children and adolescents may be chronically sleep deprived due to early school hours and constant exposure to artificial light and interactive activities. We have previously shown that sleep restriction (SR) during peripuberty impairs sperm motility and has consequences on epididymal development in rats. Thus, this study aimed to evaluate the effect of SR during peripuberty on sexual hormones and its impact on testicular tissue. Rats were subjected to 18 h of SR per day for 21 days or were maintained as controls (C) in the same room. The circulating luteinizing hormone levels were decreased in SR rats without changes in the follicle stimulating hormone levels. Plasma and intratesticular testosterone and corticosterone in the SR group were increased in relation to C group. These alterations impair testicular tissue, with decreased IL-1β, IL-6, and TNFα levels in the testis and diminished seminiferous epithelium height and Sertoli cell number. SR also increased testicular lipid peroxidation with no alteration in antioxidant profiles. There were no significant changes in sperm parameters, seminiferous tubule diameter, histopathology, spermatogenesis kinetics, neutrophil and macrophage recruitment, and IL-10 concentration. Our results show that SR unbalances sexual hormones and testicular cytokines at a critical period of sexual maturation. These changes lead to lipid peroxidation in the testes and negatively influence the testicular tissue, as evidenced by diminished seminiferous epithelium height—with apoptosis of germinative cell—and Sertoli cell number. Summary Sentence Sleep restriction unbalances sexual hormones and testicular cytokines at a critical period of sexual maturation; these changes lead to lipid peroxidation in the testes and negatively influence the testicular tissue.
TREM-1, the ideal predictive biomarker for endoscopic healing in anti-TNF-treated Crohn’s disease patients?

We read with great interest the study by Gaujoux et al , who described a whole blood marker for anti-tumour necrosis factor (TNF) responsiveness in patients with Crohn’s disease (CD). The availability of anti-TNF agents dramatically changed therapeutic strategies for patients with CD. However, an overall non-response rate of 30% has been observed, and, together with the approval of new classes of biological agents with a different mode of action, clearly indicates the need for predictive biomarkers. Gaujoux et al identified triggering receptor expressed on myeloid cells 1 ( TREM1) expression in whole blood as a biomarker for anti-TNF (non)response (higher expression in responders). 1 In inflamed colonic tissue, TREM1 expression is also decreased in future infliximab responders.1 2 TREM-1 is known to amplify inflammation, whereas TREM-1 inhibition in vivo attenuates colitis by modulating autophagy and endoplasmic reticulum (ER) stress.3 We first measured serum TREM-1 (sTREM-1) (Human sTREM-1 ELISA (HK348), Hycult Biotech, Uden, the Netherlands) in 85 patients with CD with active disease prior to anti-TNF therapy (table 1). To reduce the risk of including treatment failures secondary to immunogenicity (and not drug mechanistic failure) or non-drug-related healers, all included patients had to have a good drug exposure, defined as a maintenance trough level >3.0 µg/mL for infliximab or >5.0 µg/mL for adalimumab. Interestingly, patients who achieved mucosal healing (complete absence of ulcerations and erosions4) after 6 months of anti-TNF therapy (adalimumab and infliximab) had significantly lower baseline sTREM-1 levels compared with non-responders (50.8 pg/mL …
Estimate of the Prevalence of Anti-Gastric Parietal Cell Autoantibodies in Healthy Individuals Is Method Dependent

Objectives Anti-parietal cell antibodies (APCA) are a serologic marker of autoimmune gastritis. Their prevalence in healthy individuals is not well defined. Methods We evaluated APCA prevalence in 515 healthy blood-donors by rat/primate tissue indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and immunoblot. Results Fifty-three of 515 (10.3%) subjects were positive for APCA by at least one method: 18 only by ELISA, 10 by rodent tissue IIF, and one by primate tissue IIF; 18 were positive by ELISA and primate tissue IIF, and one by ELISA and rodent tissue IIF. Two were positive by both IIF methods, and three were triple positive. APCA positivity was confirmed by immunoblot in 100% of ELISA positive, in 95.8% of positive primate tissue IIF, and in 50% of positive rat tissue IIF. Conclusions A great discrepancy in APCA prevalence detected by different methods in this cohort was apparent. Thus, the results on APCA prevalence in healthy individuals are likely method-dependent.
miR-145-5p Inhibits Vascular Smooth Muscle Cells (VSMCs) Proliferation and Migration by Dysregulating the Transforming Growth Factor-β Signaling Cascade

Background There is accumulating evidence demonstrating that microRNAs (miRNA) play essential roles in proliferation, migration, and invasion of vascular smooth muscle cells (VSMCs). However, the exact function of these molecules and the mechanisms involved are not fully understood. In this study, we defined the role of miR-145-5p in VSMCs. Material/Methods This study used the PDGF-bb-induced VSMCs proliferation model. Expression of miR-145-5p and its target, Smad4, were detected and measured by real-time PCR and Western blot analysis. The luciferase reporter of miR-145-5p was used to elucidate miRNA-target interactions. The functions of miR-145-5p in proliferation and migration were detected by CCK-8 assay, Transwell assay, and scratch test. Results This study demonstrates that miR-145-5p is downregulated in PDGF-mediated VSMCs in both time- and dose-dependent manners. The in vitro results suggest that overexpression of miR-145-5p results in a reduction in SMAD4 and an increase in SMAD2, Smad3, and TGF-β at the mRNA and protein levels. Overexpression of miR-145-5p inhibited PDGF-induced VSMCs proliferation and migration. Moreover, SMAD4 was identified as a direct target of miR-145-5p and is involved in PDGF-mediated VSMC proliferation. Downstream factors such as Smad2, Smad3, and TGF-β were also influenced by miR-145-5p. Conclusions We identify miR-145-5p as a novel regulator of VSMC. Moreover, miR-145-5p inhibits VSMCs proliferation and migration by directly targeting Smad4 and dysregulating the transforming growth factor-β signaling cascade, including Smad2, Smad3, and TGF-β.
Sustainability of Early Intensive Behavioral Intervention for Children With Autism Spectrum Disorder in a Community Setting

This study examined whether outcomes in early intensive behavioral intervention (EIBI) during a university-led multisite project could be replicated by the same community agency independently of the project. Participants, age 18 to 75 months at onset of intervention, were 48 children with autism spectrum disorder (ASD) enrolled in 35 hr per week of publicly funded, community-based EIBI for 3 years and 46 children who were matched on baseline characteristics and received early childhood services as usual (SAU) through local early childhood special education providers. Linear mixed models indicated that EIBI participants improved significantly more than SAU participants on standardized tests of IQ, nonverbal IQ, adaptive behavior, and academic achievement, administered by independent evaluators. Although limited by the use of a matched comparison group rather than random assignment, the study provides evidence for the sustainability of effective EIBI in community settings for children with ASD who start intervention at varying ages throughout early childhood.
In vivo quantification of glial activation in minipigs overexpressing human α‐synuclein

Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha‐synuclein (α‐syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α‐syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)‐α‐[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno‐associated virus (rAAV) vectors expressing either mutant A53T α‐syn or green fluorescent protein (GFP) into the SN (4 rAAV‐α‐syn, 4 rAAV‐GFP, 5 non‐injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α‐syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α‐syn group than the control animals. We conclude that mutant α‐syn expression in the SN resulted in microglial activation in multiple sub‐ and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α‐syn in the absence of dopamine neuron degeneration.
The protease inhibitor antipain has a beneficial synergistic effect with trehalose for ram semen cryopreservation

The objective of this study was to examine the different concentrations of antipain and trehalose combination on post-thawed quality of ram semen cryopreserved in tris extender. Ejaculates were collected from four rams using the artificial vagina, pooled at 37°C and diluted with (A0 Tre0 : antipain 0 μM and trehalose 0 mM (Control); A10 Tre0 ; A50 Tre0 ; A0 Tre30 ; A0 Tre60 ; A10 Tre60 ; A10 Tre30 ; A50 Tre30 and A50 Tre60 ). Diluted semen samples were gradually cooled down from 37 to 5°C in a cold cabinet; then, they were loaded into 0.25 ml straws, frozen and stored in liquid nitrogen. Sperm motility (CASA), viability, membrane functionality and abnormality were evaluated after thawing process. Progressive motility in extender supplemented with A10 Tre0 , A0 Tre30 and A10 Tre60 significantly (p < 0.05) higher as compared to the control (A10 Tre0 ). A10 Tre60 (47.50 ± 0.73) provided the best maintenance of progressive motility in comparison with the control (40.50 ± 0.73). No significant differences were observed between all treated groups in terms of total motility, VAP, VSL, VCL, ALH, BCF, STR and LIN. The percentages of sperm with viable were significantly higher in extenders supplemented with A10 Tre0 , A50 Tre0 , A0 Tre30 and A10 Tre60 , compared to control. Addition of A10 Tre0 , A50 Tre0 and A10 Tre60 to extenders improved the percentages of sperm abnormality, compared to the controls. A10 Tre60 (67.84 ± 1.51) treatment provided the best maintenance of normal morphology compared to the other treatments. The supplementation with A10 Tre0 , A0 Tre60 and A10 Tre60 improved the percentage of sperm membrane functionality when compared to the control (p < 0.05). Comparing these results with those of control diluents, the effects of supplementation were better except for A50 Tre60 group. In conclusion, when combination of antipain (10 μM) and trehalose (30 and 60 mM) was added, they conferred a great cryosurvival capacity with their synergic effects during freeze-thawing process.
Understanding Causal Pathways in Cryptococcal Meningitis Immune Reconstitution Inflammatory Syndrome.

Affiliations: 1. Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK 2. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana 3. Botswana University of Pennsylvania Partnership, Gaborone, Botswana 4. Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA 5. Centre for Global Health, Institute for Infection and Immunity, St. George’s University of London, UK * Corresponding author: Botswana Harvard AIDS Institute Partnership, Private Bag BO320, Gaborone, BOTSWANA. Email: joseph.jarvis@lshtm.ac. uk
Distinct Cognitive and Brain Morphological Features in Healthy Subjects Unaware of Informant-Reported Cognitive Decline

Background: Subtle cognitive decline preceding cognitive impairment can be self-perceived, referred to as subjective cognitive decline (SCD), or go unrecognized. Objective: To study the clinical, cognitive, and structural neuroimaging characteristics of psychometrically normal subjects without self-awareness of cognitive decline (unaware decliners, UD) and to compare them with SCD participants and controls. Methods: 2,640 participants from the ALFA cohort, 1,899 controls, 173 UD (decline reported by the informant only), and 568 SCD underwent clinical and cognitive explorations. A subset of 530 underwent structural MRI (379 Controls; 43 UD; 108 SCD). Linear models adjusting for confounders (age, sex, education, and mood state) were used to assess group differences on cognition and voxel-wise grey matter (GM) volumes. Results: 6.6% were UD while 21.5% SCD. No differences in anxiety and depression were observed between controls and UD, while SCD did (p < 0.01). UD showed lower performance in the Memory Binding Test free recall (p < 0.005) than controls, but no differences compared to SCD. Right medial frontal and insular increments of GM volumes were observed in UD with respect to controls. Informant report of decline in UD and SCD was associated with lower left hippocampal GM volume but related to memory performance only in UD (rho = 0.46, p = 0.002). Conclusions: UD had worse memory performance than controls which correlated with hippocampal GM volume and presented brain volume increments in self-appraisal areas (medial frontal and insula). Individuals unaware of cognitive decline may represent a distinct group at risk for cognitive impairment and support the usefulness of informant-reported cognitive decline.
Light and scanning electron microscopy of the tongue of the sand lizard (Lacerta agilis).

BACKGROUND Despite the fact that numerous reptile species are widely studied by the researchers, information describing the detailed structure of particular organs in many reptiles is missing. MATERIALS AND METHODS The tongue of the sand lizard (Lacerta agilis) was examined under the light and scanning electron microscope. It is divided into bifurcated apex, corpus and bifurcated radix. The tip of the lingual apex is devoid of lingual papillae. RESULTS The remaining dorsal surface of the tongue bears either fused papillae in the form of caudally directed ridges or individual papillae represented by mu- shroom-like or semilunar prominences (lingual apex) or fish scale-like papillae (lingual corpus) and horizontally laid ridges extending in the form of lobulated prominences (lingual corpus, lingual radix). Regardless of the shape, lingual papillae contain numerous muscle fibres and they are all considered to be mechanical. The lingual epithelium changes from the simple squamous into stratified squamous in the caudal direction. No salivary glands or sensory structures were recognised. CONCLUSIONS This description is to be used mainly for comparative studies. It could also help to understand how different lizards capture the pray.
Attachment Disorder behavior in early and middle childhood: associations with children’s self-concept and observed signs of negative internal working models

ABSTRACT Most research on attachment in childhood is based on observation. In contrast, research on reactive attachment disorder (RAD) is mainly based on caregiver reports. Moreover, little is known about self-concept or internal working models (IWMs) of self and others in children with RAD. The present study examined whether caregiver reports and the frequency of observed signs of RAD reveal differences between children at risk for developing RAD symptoms and healthy controls in middle childhood. In addition, children’s self-concept, observable signs of negative IWMs, and mental health were assessed. Results revealed that the RAD risk group showed increased reported and observed signs of RAD, a more negative self-concept, and more signs of negative IWMs compared to healthy controls. Signs of RAD in middle childhood were expressed trans-relational to both caregivers and strangers. Moreover, RAD symptoms were associated with negative self-concept, observed signs of negative IWMs, and poor mental health.
Nurses’ Attitudes toward, and Needs for Online Learning: Differences between Rural and Urban Hospitals in Shanghai, East China

Health professionals need continuing education to maintain their qualifications and competency. Online learning increases the accessibility and flexibility of continuing education. Assessment of nurses’ attitudes toward, and needs for, online learning can provide suggestions regarding learning program design and delivery. This study aimed to evaluate Chinese nurses’ attitudes toward, and needs for, online learning, and to explore the differences in attitudes and needs between nurses working in rural and urban hospitals. This work is a secondary analysis of a multicenter cross-sectional study conducted in Shanghai in 2015 (n = 550). Multiple regression techniques were used to determine the factors associated with nurses’ attitudes toward, and needs for, online learning. Results showed that nurses in rural hospitals had more positive attitudes toward online learning (102.7 ± 14.2) than those in urban hospitals (98.3 ± 12.9) (p < 0.001). For rural hospitals, nurses who could use computers and access the internet in their workplace reported more positive attitudes than those who could not. For urban hospitals, nurse educators showed significantly more positive attitudes than others. Communication skills (86.5%) and patient education (86.3%) were the most commonly-reported learning needs for nurses regardless of their working settings. Chinese nurses were willing to adopt online learning as a continuing education method. Nurses working in rural hospitals displayed more positive attitudes toward, and needs for, online learning than those working in urban hospitals. Nursing educators and managers should develop online learning programs and provide appropriate support to fulfill nurses’ learning needs, especially for those working in rural healthcare settings.