Miracle-dz/UniFAR-FTUs huggingface dataset:
Examining 3-month test-retest reliability and reliable change using the Cambridge Neuropsychological Test Automated Battery

Abstract The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a battery of computerized neuropsychological tests commonly used in Europe in neurology and psychiatry studies, including clinical trials. The purpose of this study was to investigate test-retest reliability and to develop reliable change indices and regression-based change formulas for using the CANTAB in research and practice involving repeated measurement. A sample of 75 healthy adults completed nine CANTAB tests, assessing three domains (i.e., visual learning and memory, executive function, and visual attention) twice over a 3-month period. Wilcoxon signed-rank tests showed significant practice effects for 6 of 14 outcome measures with effect sizes ranging from negligible to medium (Hedge’s g: .15–.40; Cliff’s delta: .09–.39). The Spatial Working Memory test, Attention Switching Task, and Rapid Visual Processing test were the only tests with scores of adequate test-retest reliability. For all outcome measures, Pearson’s and Spearman’s correlation coefficients ranged from . 39 to . 79. The measurement error surrounding difference scores was large, thus requiring large changes in performance (i.e., 1–2 SDs) in order to interpret a change score as reliable. In the regression equations, test scores from initial testing significantly predicted retest scores for all outcome measures. Age was a significant predictor in several of the equations, while education was a significant predictor in only two of the equations. The adjusted R 2 values ranged between . 19 and . 67. The present study provides results enabling clinicians to make probabilistic statements about change in cognitive functions based on CANTAB test performances.
Comparative Evaluation of Two Antioxidants on Reversing the Immediate Bond Strength of Bleached Enamel: In Vitro Study

Background Tooth bleaching causes a significant decrease in the bonding strength between the resin and human enamel. Nevertheless, the effects of different antioxidant types on the immediate bonding strength of resin and bleached enamel were significantly different. Therefore, the objective of this study was to compare the effects of 2 antioxidants for enhancing the bond strength of the resin to bleached enamel. Material/Methods There were 48 enamel blocks performed from 48 recently extracted maxillary central incisors. There were 8 groups: NC (negative control, no bleached specimens restored without antioxidants); NA (no antioxidant, bleached specimens bonded immediately without any antioxidants); SA30, SA60, and SA120 (bleached specimens accepted the management of 10% sodium ascorbate (SA) for 30 minutes, 60 minutes, and 120 minutes, respectively, before restored); PC30, PC60, and PC120 (bleached specimens received treatment of 5% proanthocyanidins (PC) for 30 minutes, 60 minutes, and 120 minutes, respectively, before restored). We measured the micro-tensile bond strength of specimens and used 2-way ANOVA to analyze the data. Results The mean±standard deviation bond strength measured were: NC, 29.99±4.00; NA, 14.90±1.97; SA30, 18.60±2.20; SA60, 22.57±2.71; SA120, 26.15±3.85; PC30, 16.78±2.29; PC60, 19.13±2.24, PC120, 23.90±2.01 MPa. In addition, the fracture types were mainly of an adhesive mode (88.75%), followed by mixed (7.5%), and cohesive (3.75%). Conclusions 10% sodium ascorbate provided a comparatively more promising improvement for immediate bond strength than 5% proanthocyanidins when the same duration of antioxidant was applied.
The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Purpose To determine the role of autophagy in the innate immune response to fungal keratitis (FK) caused by Aspergillus fumigatus infection. Methods Corneal samples obtained from patients and mice with FK were visualized via transmission electron microscopy (TEM). Autophagy-related proteins LC3B-II, Beclin-1, LAMP-1, and p62 in A. fumigatus-infected corneas of C57BL/6 mice were tested by Western blot. After treatment with autophagy inhibitors 3-methyladenine (3-MA), chloroquine (CQ), or inducer rapamycin, autophagy-related proteins were detected by Western blot. Corneas were photographed with slit lamp microscopy and pathological changes were observed by hematoxylin and eosin staining. Polymorphonuclear neutrophilic leukocytes (PMNs) were assessed by immunofluorescent staining and observed under TEM. The levels of CXCL-1, IL-1β, HMGB1, IL-18, TNF-α, and IL-10 were tested by reverse transcription polymerase chain reaction and Western blot. The quantification of fungal loads was detected and photographed. Results The accumulation of autophagosomes in corneas of patients and mice with FK was observed with TEM. The expression of LC3B-II, Beclin-1, and LAMP-1 was elevated in corneas after fungal infection, whereas p62 was reduced. Treatment with 3-MA or CQ upregulated clinical scores, pathological changes, and the expression of CXCL-1, IL-1β, HMGB1, IL-18, and TNF-α except IL-10. The morphology of PMNs was changed and PMN recruitment was increased in mice corneas treated with 3-MA or CQ, whereas rapamycin reduced the inflammatory response to keratitis. These results were statistically significant. Conclusions A. fumigatus infection increases the expression of autophagy in corneas. Autophagy plays an anti-inflammatory role in the innate immune response to A. fumigatus keratitis.
The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

The ability of Streptococcus gordonii to cope with oxidative stress is important for survival and persistence in dental plaque. In this study, we used mutational, phenotypic, and biochemical approaches to characterize the role of a methionine sulfoxide reductase (MsrAB) and proteins encoded by genes in the msrAB operon and an adjacent operon in oxidative stress tolerance in S. gordonii. The results showed that MsrAB and four other proteins encoded in the operons are needed for protection from H2O2 and methionine sulfoxide. These five proteins formed a reducing pathway that was needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice. In the pathway, MsrAB was the enzyme that repaired oxidatively damaged proteins, and the two thioredoxin-like lipoproteins (SdbB and Sgo_1177) and two CcdA proteins were proteins that maintained the catalytic cycle of MsrAB. Consistent with the role in oxidative stress tolerance, the production of MsrAB, SdbB, and Sgo_11777 was induced in aerobic growth and planktonic cells.
Slit2 May Underlie Divergent Induction by Thyrotropin of IL-23 and IL-12 in Human Fibrocytes

Key Points Slit2, a neuron repellant, can determine fibrocyte cytokine expression repertoires. Slit2 attenuates IL-23 while enhancing IL-12. Divergent IL-23 and IL-12 expression is mediated through JNK. IL-23 and IL-12, two structurally related heterodimeric cytokines sharing a common subunit, divergently promote Th cell development and expansion. Both cytokines have been implicated in the pathogenesis of thyroid-associated ophthalmopathy (TAO), an autoimmune component of Graves disease. In TAO, CD34+ fibrocytes, putatively derived from bone marrow, can be identified in the orbit. There they masquerade as CD34+ orbital fibroblasts (OF) (CD34+ OF) and cohabitate with CD34− OF in a mixed fibroblast population (GD-OF). Slit2, a neural axon repellent, is expressed and released by CD34− OF and dampens the inflammatory phenotype of fibrocytes and CD34+ OF. In this study we report that thyrotropin (TSH) and the pathogenic, GD-specific monoclonal autoantibody, M22, robustly induce IL-23 in human fibrocytes; however, IL-12 expression is essentially undetectable in these cells under basal conditions or following TSH-stimulation. In contrast, IL-12 is considerably more inducible in GD-OF, cells failing to express IL-23. This divergent expression and induction of cytokines appears to result from cell type–specific regulation of both gene transcription and mRNA stabilities. It appears that the JNK pathway activity divergently attenuates IL-23p19 expression while enhancing that of IL-12p35. The shift from IL-23p19 expression in fibrocytes to that of IL-12p35 in their derivative CD34+ OF results from the actions of Slit2. Thus, Slit2 might represent a molecular determinant of balance between IL-23 and IL-12 expression, potentially governing immune responses in TAO.
Endophytic Bacterial Microbiome Diversity in Early Developmental Stage Plant Tissues of Wheat Varieties

Endophytic bacteria are an important part of different functions in plants that lead to plants’ production characteristics as well as their stress response mechanisms. Endophytic bacterial diversity was analyzed in this study to describe 16S rRNA variability and changes in the leaves of drought-tolerant and drought-susceptible wheat when growth under in vitro conditions. A metagenomic analysis was applied and a pilot exploratory study was performed to prove this type of analysis as applicable to tracking endophytic bacterial diversity changes when a drought stress is applied to an in vitro culture of wheat. The study showed that the changes in the bacterial endophytes’ variabilities associated preferentially with the drought stress varietal characteristics of the analyzed wheat instead of the applied stress conditions.
Age and sex as confounding factors in the relationship between cardiac mitochondrial function and type 2 diabetes in the Nile Grass rat

Our study revisits the role of cardiac mitochondrial adjustments during the progression of type 2 diabetes mellitus (T2DM), while considering age and sex as potential confounding factors. We used the Nile Grass rats (NRs) as the animal model. After weaning, animals were fed either a Standard Rodent Chow Diet (SRCD group) or a Mazuri Chinchilla Diet (MCD group) consisting of high-fiber and low-fat content. Both males and females in the SRCD group, exhibited increased body mass, body mass index, and plasma insulin compared to the MCD group animals. However, the females were able to preserve their fasting blood glucose throughout the age range on both diets, while the males showed significant hyperglycemia starting at 6 months in the SRCD group. In the males, a higher citrate synthase activity—a marker of mitochondrial content—was measured at 2 months in the SRCD compared to the MCD group, and this was followed by a decline with age in the SRCD group only. In contrast, females preserved their mitochondrial content throughout the age range. In the males exclusively, the complex IV capacity expressed independently of mitochondrial content varied with age in a diet-specific pattern; the capacity was elevated at 2 months in the SRCD group, and at 6 months in the MCD group. In addition, females, but not males, were able to adjust their capacity to oxidize long-chain fatty acid in accordance with the fat content of the diet. Our results show clear sexual dimorphism in the variation of mitochondrial content and oxidative phosphorylation capacity with diet and age. The SRCD not only leads to T2DM but also exacerbates age-related cardiac mitochondrial defects. These observations, specific to male NRs, might reflect deleterious dietary-induced changes on their metabolism making them more prone to the cardiovascular consequences of aging and T2DM.
Evaluation of Quantitative Relationship Between Target Expression and Antibody-Drug Conjugate Exposure Inside Cancer Cells

Antibody-drug conjugates (ADCs) employ overexpressed cell surface antigens to deliver cytotoxic payloads inside cancer cells. However, the relationship between target expression and ADC efficacy remains ambiguous. In this manuscript, we have addressed a part of this ambiguity by quantitatively investigating the effect of antigen expression levels on ADC exposure within cancer cells. Trastuzumab-valine-citrulline-monomethyl auristatin E was used as a model ADC, and four different cell lines with diverse levels of human epidermal growth factor receptor 2 (HER2) expression were used as model cells. The pharmacokinetics (PK) of total trastuzumab, released monomethyl auristatin E (MMAE), and total MMAE were measured inside the cells and in the cell culture media following incubation with two different concentrations of ADC. In addition, target expression levels, target internalization rate, and cathepsin B and MDR1 protein concentrations were determined for each cell line. All the PK data were mathematically characterized using a cell-level systems PK model for ADC. It was found that SKBR-3, MDA-MB-453, MCF-7, and MDA-MB-468 cells had ∼800,000, ∼250,000, ∼50,000, and ∼10,000 HER2 receptors per cell, respectively. A strong linear relationship (R2 > 0.9) was observed between HER2 receptor count and released MMAE exposure inside the cancer cells. There was an inverse relationship found between HER2 expression level and internalization rate, and cathepsin B and multidrug resistance protein 1 (MDR1) expression level varied slightly among the cell lines. The PK model was able to simultaneously capture all the PK profiles reasonably well while estimating only two parameters. Our results demonstrate a strong quantitative relationship between antigen expression level and intracellular exposure of ADCs in cancer cells. SIGNIFICANCE STATEMENT In this manuscript, we have demonstrated a strong linear relationship between target expression level and antibody-drug conjugate (ADC) exposure inside cancer cells. We have also shown that this relationship can be accurately captured using the cell-level systems pharmacokinetics model developed for ADCs. Our results indirectly suggest that the lack of relationship between target expression and efficacy of ADC may stem from differences in the pharmacodynamic properties of cancer cells.
Treatment and disease‐related complications in multiple myeloma: Implications for survivorship

New treatments have transformed multiple myeloma into a chronic disease. Hence, optimal management of treatment and disease‐related complications remains a critical component of survivorship care. Survivorship care model in cancers requiring a fixed‐duration therapy may not be applicable to myeloma, since patients are exposed to multiple lines of continuous therapy along the disease trajectory. The two most common therapy‐related causes of death, which require special consideration, are infection and second cancers. Identifying patients at a high risk of toxicities will facilitate individualized treatment selection and designing clinical trials for protective strategies targeting those patients. For example, prophylactic antibiotic or immunoglobulin replacement can be tested for primary prevention of infections in high‐risk patients. Long‐term follow up of ongoing trials and epidemiologic data will help identify the nature and trajectory of rare toxicities with a long latency, such as secondary cancers. Patients who are frail, have persistent renal insufficiency, and refractory to multiple lines of therapy need special attention regarding treatment toxicity and quality of life. In this review, we discuss the incidence, risk‐factors, and management of treatment and disease‐related complications in myeloma, discuss knowledge gaps and research priorities in this area, and propose a survivorship care model to improve health‐care delivery to a growing pool of myeloma survivors.
Fatty liver is not independently associated with the rates of complete response to oral antiviral therapy in chronic hepatitis B patients

Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression ([CVS], HBV DNA <20‐100 IU/mL) and/or biochemical response ([BR], ALT of ≤25 U/L for females; 35 U/L for males) in CHB patients who received oral antiviral therapy.
Drawing a line in the sand: affect and testimony in autism assessment teams in the UK

Abstract Diagnosis of autism in the UK is generally made within a multidisciplinary team setting and is primarily based on observation and clinical interview. We examined how clinicians diagnose autism in practice by observing post‐assessment meetings in specialist autism teams. Eighteen meetings across four teams based in the south of England and covering 88 cases were audio‐recorded, transcribed and analysed using thematic analysis. We drew out two themes, related to the way in which clinicians expressed their specialist disciplinary knowledge to come to diagnostic consensus: Feeling Autism in the Encounter; and Evaluating Testimonies of Non‐present Actors. We show how clinicians produce objective accounts through their situated practices and perform diagnosis as an act of interpretation, affect and evaluation to meet the institutional demands of the diagnostic setting. Our study contributes to our understanding of how diagnosis is accomplished in practice.
Long non‐coding RNA PRRT3‐AS1 silencing inhibits prostate cancer cell proliferation and promotes apoptosis and autophagy

What is the central question of this study? What is the role of lncRNA PRRT3‐AS1 in the regulation of peroxisome proliferator‐activated receptor γ (PPARγ) gene‐mediated mechanistic target of rapamycin (mTOR) signalling pathway in proliferation, apoptosis and autophagy of prostate cancer cells? What is the main finding and its importance? The targeting relation between lncRNA PRRT3‐AS1 and PPARγ was verified, and it was demonstrated that silencing of lncRNA PRRT3‐AS1 can upregulate apoptosis and autophagy yet downregulate proliferation, migration and invasion of prostate cancer cells through the mTOR signalling pathway. Further work is needed to consolidate the therapeutic value of lncRNA PRRT3‐AS1 in clinical trials and treatment of prostate cancer.
In Utero Exposures to Electronic-Cigarette Aerosols Impair the Wnt Signaling during Mouse Lung Development.

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine-cinnamon flavored e-cig aerosols for 14 to 31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered-air. Sub-groups of offspring were sacrificed at birth or at 4 weeks of age. Compared to respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were down-regulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the down-regulation of 75 lung genes involved in the Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.
The Vacuolar H+ ATPase α3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells

Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H+ ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness of some cancers, yet often on the basis of unspecific inhibitors. Serving as a membrane anchor directing V-ATPase localization, the a subunit of the V0 domain of the V-ATPase (ATP6V0a1-4) is particularly interesting in this regard. Here, we map the regulation and roles of ATP6V0a3 in migration, invasion, and growth in pancreatic ductal adenocarcinoma (PDAC) cells. a3 mRNA and protein levels were upregulated in PDAC cell lines compared to non-cancer pancreatic epithelial cells. Under control conditions, a3 localization was mainly endo-/lysosomal, and its knockdown had no detectable effect on pHi regulation after acid loading. V-ATPase inhibition, but not a3 knockdown, increased HIF-1α expression and decreased proliferation and autophagic flux under both starved and non-starved conditions, and spheroid growth of PDAC cells was also unaffected by a3 knockdown. Strikingly, a3 knockdown increased migration and transwell invasion of Panc-1 and BxPC-3 PDAC cells, and increased gelatin degradation in BxPC-3 cells yet decreased it in Panc-1 cells. We conclude that in these PDAC cells, a3 is upregulated and negatively regulates migration and invasion, likely in part via effects on extracellular matrix degradation.
Microstructure of Nonjuxtapapillary Microvasculature Dropout in Healthy Myopic Eyes

Purpose The purpose of this study was to characterize the microstructure of the nonjuxtapapillary microvasculature dropout (MvD) in healthy myopic eyes. Methods This cross-sectional study included 50 eyes (25 eyes with a nonjuxtapapillary MvD and 25 age-matched eyes without any MvD) from a cohort of 126 nonglaucomatous healthy myopic eyes having parapapillary atrophy (PPA) γ-zone. The parapapillary deep-layer microvasculature was evaluated in en-face images obtained using swept-source optical coherence tomography (OCT) angiography (OCTA). A nonjuxtapapillary MvD was defined as an area with focal absence of vascular signals in the distal portion of PPA confined to the nonjuxtapapillary area. Enhanced depth-imaging OCT scanning was performed to assess the parapapillary microstructure. Results Nonjuxtapapillary MvD was found in 25 eyes (19.8%). The parapapillary microstructure at the nonjuxtapapillary MvD in 18 eyes was characterized by the misalignment of Bruch's membrane (BM)–retinal pigment epithelium (RPE) complex, which was identified by the absence of BM-RPE complex and the presence of the inner retina and sclera. In seven eyes with a nonjuxtapapillary MvD but without such misaligned BM-RPE complex, RPE atrophy was observed at the location of the nonjuxtapapillary MvD. Eyes with a nonjuxtapapillary MvD had a longer axial length (AXL; P = 0.013) and a wider γ-zone (P < 0.001) than age-matched control eyes without any MvD. Conclusions The microstructure at the nonjuxtapapillary MvD in healthy myopic eyes was characterized in approximately 70% of eyes by temporally misaligned BM-RPE complex. Although the clinical importance of the nonjuxtapapillary MvD remains to be determined, it should be differentiated from the parapapillary choroidal MvD observed in glaucoma.