Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models

Ovarian cancer often has a poor clinical prognosis because of late detection, frequently after metastatic progression, as well as acquired resistance to taxane-based therapy. Herein, we evaluate a novel class of covalent microtubule stabilizers, the C-22,23-epoxytaccalonolides, for their efficacy against taxane-resistant ovarian cancer models in vitro and in vivo. Taccalonolide AF, which covalently binds β-tubulin through its C-22,23-epoxide moiety, demonstrates efficacy against taxane-resistant models and shows superior persistence in clonogenic assays after drug washout due to irreversible target engagement. In vivo, intraperitoneal administration of taccalonolide AF demonstrated efficacy against the taxane-resistant NCI/ADR-RES ovarian cancer model both as a flank xenograft, as well as in a disseminated orthotopic disease model representing localized metastasis. Taccalonolide-treated animals had a significant decrease in micrometastasis of NCI/ADR-RES cells to the spleen, as detected by quantitative RT-PCR, without any evidence of systemic toxicity. Together, these findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients.
Caries and Restoration Detection Using Bitewing Film Based on Transfer Learning with CNNs

Caries is a dental disease caused by bacterial infection. If the cause of the caries is detected early, the treatment will be relatively easy, which in turn prevents caries from spreading. The current common procedure of dentists is to first perform radiographic examination on the patient and mark the lesions manually. However, the work of judging lesions and markings requires professional experience and is very time-consuming and repetitive. Taking advantage of the rapid development of artificial intelligence imaging research and technical methods will help dentists make accurate markings and improve medical treatments. It can also shorten the judgment time of professionals. In addition to the use of Gaussian high-pass filter and Otsu’s threshold image enhancement technology, this research solves the problem that the original cutting technology cannot extract certain single teeth, and it proposes a caries and lesions area analysis model based on convolutional neural networks (CNN), which can identify caries and restorations from the bitewing images. Moreover, it provides dentists with more accurate objective judgment data to achieve the purpose of automatic diagnosis and treatment planning as a technology for assisting precision medicine. A standardized database established following a defined set of steps is also proposed in this study. There are three main steps to generate the image of a single tooth from a bitewing image, which can increase the accuracy of the analysis model. The steps include (1) preprocessing of the dental image to obtain a high-quality binarization, (2) a dental image cropping procedure to obtain individually separated tooth samples, and (3) a dental image masking step which masks the fine broken teeth from the sample and enhances the quality of the training. Among the current four common neural networks, namely, AlexNet, GoogleNet, Vgg19, and ResNet50, experimental results show that the proposed AlexNet model in this study for restoration and caries judgments has an accuracy as high as 95.56% and 90.30%, respectively. These are promising results that lead to the possibility of developing an automatic judgment method of bitewing film.
The Q-Pass Index: A Multifactorial IMUs-Based Tool to Assess Passing Skills in Basketball

Despite being a key sport-specific characteristic in performance, there is no practical tool to assess the quality of the pass in basketball. The aim of this study is to develop a tool (the quality-pass index or Q-Pass) able to deliver a quantitative, practical measure of passing skills quality based on a combination of accuracy, execution time and pass pattern variability. Temporal, kinematics and performance parameters were analysed in five different types of passes (chest, bounce, crossover, between-the-leg and behind-the-back) using a field-based test, video cameras and body-worn inertial sensors (IMUs). Data from pass accuracy, time and angular velocity were collected and processed in a custom-built excel spreadsheet. The Q-pass index (0–100 score) resulted from the sum of the three factors. Data were collected from 16 young basketball players (age: 16 ± 2 years) with high (experienced) and low (novice) level of expertise. Reliability analyses found the Q-pass index as a reliable tool in both novice (CV from 4.3 to 9.3%) and experienced players (CV from 2.8 to 10.2%). Besides, important differences in the Q-pass index were found between players’ level (p < 0.05), with the experienced showing better scores in all passing situations: behind-the-back (ES = 1.91), bounce (ES = 0.82), between-the-legs (ES = 1.11), crossover (ES = 0.58) and chest (ES = 0.94). According to these findings, the Q-pass index was sensitive enough to identify the differences in passing skills between young players with different levels of expertise, providing a numbering score for each pass executed.
Refining the amyloid β peptide and oligomer fingerprint ambiguities in Alzheimer’s disease: Mass spectrometric molecular characterization in brain, cerebrospinal fluid, blood, and plasma

Since its discovery, amyloid‐β (Aβ) has been the principal target of investigation of in Alzheimer's disease (AD). Over the years however, no clear correlation was found between the Aβ plaque burden and location, and AD‐associated neurodegeneration and cognitive decline. Instead, diagnostic potential of specific Aβ peptides and/or their ratio, was established. For instance, a selective reduction in the concentration of the aggregation‐prone 42 amino acid‐long Aβ peptide (Aβ42) in cerebrospinal fluid (CSF) was put forward as reflective of Aβ peptide aggregation in the brain. With time, Aβ oligomers—the proposed toxic Aβ intermediates—have emerged as potential drivers of synaptic dysfunction and neurodegeneration in the disease process. Oligomers are commonly agreed upon to come in different shapes and sizes, and are very poorly characterized when it comes to their composition and their “toxic” properties. The concept of structural polymorphism—a diversity in conformational organization of amyloid aggregates—that depends on the Aβ peptide backbone, makes the characterization of Aβ aggregates and their role in AD progression challenging. In this review, we revisit the history of Aβ discovery and initial characterization and highlight the crucial role mass spectrometry (MS) has played in this process. We critically review the common knowledge gaps in the molecular identity of the Aβ peptide, and how MS is aiding the characterization of higher order Aβ assemblies. Finally, we go on to present recent advances in MS approaches for characterization of Aβ as single peptides and oligomers, and convey our optimism, as to how MS holds a promise for paving the way for progress toward a more comprehensive understanding of Aβ in AD research.
Clinical and radiological characteristics of older‐adult‐onset Alexander disease

Alexander disease (ALXDRD) affects a wide range of ages from infancy to adulthood. However, only a few cases involving patients with older‐adult onset over 65 years of age have been reported. In contrast, regarding in‐house data, 10.6% of 85 cases with the identification of GFAP mutations demonstrated older‐adult onset. This discrepancy may be due to poor awareness of such cases.
Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling

The heavy metal Cadmium (Cd), a widespread environmental contaminant, poses serious hazards to human health and is considered a metallohormone and carcinogen. In women with uterine fibroids, there is a significant association between blood Cd levels and increased fibroid tumor size. The aim of this study was to determine if benign human uterine leiomyoma (fibroid) cells could be malignantly transformed in vitro by continuous Cd exposure and, if so, explore a molecular mechanism by which this could occur. We found when fibroid cells were exposed to 10 µM CdCl2 for 8 weeks, a robust and fast‐growing Cd‐Resistant Leiomyoma (CR‐LM) cell culture was established. The CR‐LM cells formed viable colonies in soft agar and had increased cytoplasmic glycogen aggregates, enhanced cell motility, a higher percentage of cells in G2/M phase, and increased expression of the proliferation marker Ki‐67. NanoString analysis showed downregulation of genes encoding for extracellular matrix (ECM) components, such as collagens, fibronectins, laminins, and SLRP family proteins, whereas genes involved in ECM degradation (MMP1, MMP3, and MMP10) were significantly upregulated. A volcano plot showed that the top differentially genes favored cancer progression. Functional analysis by ingenuity pathway analysis predicted a significant inhibition of TGFB1 signaling, leading to enhanced proliferation and attenuated fibrosis. Prolonged Cd exposure altered phenotypic characteristics and dysregulated genes in fibroid cells predicative of progression towards a cancer phenotype. Therefore, continuous Cd exposure alters the benign characteristics of fibroid cells in vitro, and Cd exposure could possibly pose a health hazard for women with uterine fibroids.
Clinical efficacy of single and multiple applications of antimicrobial photodynamic therapy in periodontal maintenance: A systematic review and network meta-analysis.

BACKGROUND At present the clinical efficacy of single (S) versus multiple (M) applications of antimicrobial photodynamic therapy (aPDT) is controversially discussed. AIM To systematically evaluate the clinical efficacy of adjunctive S and M applications of aPDT to subgingival debridement (SD) in the treatment of residual periodontal pockets. METHODS An electronic search was carried out for randomized controlled clinical trials (RCTs) reporting on SD with the adjunctive use of S- or M-aPDT applications. RESULTS Statistically significantly higher improvement in bleeding on probing (BOP) and probing depth (PD) reduction was found for SD + S-aPDT versus SD, with Mean difference (MD) = -16.8 (95% CI: -30.7 to -2.91; p = 0.02) and 0.4, (95% CI: 0.02 to 0.78, p = 0.04), respectively. Regarding BOP, there was also a statistically significant difference when SD + M-aPDT was compared with SD alone, with a MD of -5.13 (95% CI: -7.20 to -3.07; p < 0.00001). For all parameters, SD + S-aPDT demonstrated the best treatment ranking of probability results, followed by SD + M-aPDT and SD alone. CONCLUSIONS Within their limits, the present data indicate that in periodontal patients enrolled in maintenance: a) single and multiple adjunctive applications of aPDT following SD resulted in statistically significant BOP reduction compared to SD alone, and b) repeated applications of aPDT did not seem to result in superior outcomes compared to single applications.
Total vitamin D intake and risks of early-onset colorectal cancer and precursors.

BACKGROUND & AIMS Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratio (OR) and 95% CI for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = 0.01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.
Densities of melts in the CaO-MgO-Al2O3-SiO2 system

Abstract Density measurements have been performed on 4 Mg-aluminosilicate melts and 4 melts in the CaO-MgO-Al2O3-SiO2 system (including stoichiometries corresponding to the mineral compositions a°kermanite, diopside, enstatite, and cordierite) in the temperature ranges from their respective melting points up to 1800 °C, using the very precise Ir-based doublebob Archimedean method. The measured densities of the melts range from 2.67 to 2.42 g/cm3. Together with our previous density measurements in the CaO-Al2O3-SiO2 system, the present results were analyzed using a regression equation, including a non-ideal mixing term between CaO and SiO2, from which the partial molar volume of each oxide liquid component was obtained by the method of least squares. This procedure yields partial molar volumes of 12.66, 20.66, 36.67, 27.30 cm3/mol at 1873 K for MgO, CaO, Al2O3, and SiO2, respectively. A calculation scheme for melts in the CaO-MgO-Al2O3-SiO2 system is proposed, involving an excess volume term between SiO2 and CaO that is capable of reproducing the liquid molar volumes to within 1% except for extremely Ca-, Mg-, and Al-rich compositions. Better constraints on melt volumes in those extreme composition ranges requires new very high-temperature data. The volume of fusion of various minerals was calculated and implications for the structure of their respective melts are also discussed. In addition, the volumes of fusion from this study are also compared to that obtained using the Clausius-Clapeyron equation.
Low dosage sulfite pretreatment in a modern TMP-line

The effects of low dosage sulfite pretreatment combined with modern high consistency double disc refining were evaluated for production of thermomechanical pulp in a mill scale trial using Norway spruce wood at the Braviken paper mill (Holmen Paper AB, Sweden). Spruce wood chips were mechanically pretreated in an Impressafiner before impregnation with different dosages (0-1.2%) of sodium sulfite (Na2SO3) at pH 9. Approximately 23% of the added sulfite was converted to sulfonate groups in pulp, resulting in a sulfonate content of 0-0.28% (as Na2SO3). The low dosage sulfite addition increased tensile index, elongation, density, brightness and decreased shive content, light scattering and light absorption coefficients when compared at equal specific energy consumption (SEC). The increase in tensile index was proportional to dosage of sulfite. Further analyses showed that low dosage sulfite addition did not affect the distribution of the Bauer-McNett fractions nor the fibre length for pulps refined with equal SEC. However, the low dosage sulfite addition increased fibre delamination/internal fibrillation (D/IF). With the addition of 1.2% Na2SO3, it was possible to produce pulp with a tensile index of 47 Nm/g using ~320 kWh/bdt (~15%) lower refining energy, compared with pulps produced without sulfite addition.
Adsorption of 2‐Chlorophenol on the Surface of Silica‐ and Alumina‐Supported Iron Oxide: An FTIR and XPS Study

The adsorption of 2‐chlorophenol (2‐CPh) on the surface of silica, alumina and silica‐ and alumina‐supported iron oxides was examined at 30 and 250 °C. The formation of a chlorophenolate carbanion/chlorophenoxy radical intermediate on the surface of silica and alumina surfaces is identified by using in situ FTIR spectroscopy. The IR spectra of 2‐CPh adsorbed on supported iron oxide at 250 °C highlight significant differences in the adsorption complex between 2‐CPh and the two supported iron oxides (on silica and alumina). Under conditions of the low coverage of 2‐CPh on the surface of these catalysts, FTIR spectroscopy was used to indicate that the adsorption of 2‐CPh on the surface of silica‐supported iron oxide commences with the formation of a chlorophenolate species, whereas 2‐CPh creates a surface formate species on alumina‐supported iron oxide. Moreover, the strong bonds of 2‐CPh and a high concentration of the carbonate species are evident on the alumina surfaces by using both FTIR and X‐ray photoelectron spectroscopy.
Debunking Misinformation About Genetically Modified Food Safety on Social Media: Can Heuristic Cues Mitigate Biased Assimilation?

Focusing on debunking misinformation about genetically modified (GM) food safety in a social media context, this study examines whether source cues and social endorsement cues interact with individuals’ preexisting beliefs about GM food safety in influencing misinformation correction effectiveness. Using an experimental design, this study finds that providing corrective messages can effectively counteract the influence of misinformation, especially when the message is from an expert source and receives high social endorsements. Participants evaluate misinformation and corrective messages in a biased way that confirms their preexisting beliefs about GM food safety. However, their initial misperceptions can be reduced when receiving corrective messages.
Postprandial effects of a whey protein-based multi-ingredient nutritional drink compared with a normal breakfast on glucose, insulin, and active GLP-1 response among type 2 diabetic subjects: a crossover randomised controlled trial

Abstract Postprandial hyperglycaemia is recognised as an important target in type 2 diabetes management. Dietary pattern, meal composition, and amount of food intake are major factors for maintaining postprandial blood glucose levels. The aim of this study was to investigate the effect of consuming a whey protein-based multi-ingredient nutritional drink (WD) on postprandial glycaemic, insulinaemic, and active glucagon-like peptide-1 (GLP-1) responses in comparison to a typical breakfast, which is boiled white rice with chicken (BC) in patients with type 2 diabetes mellitus (T2DM). Fifteen subjects with T2DM participated in a randomised, controlled, cross-over study. Two isocaloric diets with similar nutrient composition were randomly tested with at least 7 d in between. Glucose, insulin, and active GLP-1 were measured by standard methods with blood samples collected with a venous catheter for 240 min during a kinetic test. The incremental area under the curve (iAUC0–240 min) for plasma glucose was significantly lower after the consumption of WD (WD: 3551 ± 546; BC: 9610 ± 848 mg min/dl; P < 0⋅01), while insulinaemic response tended to be lesser (iAUC0–240 min) than those of BC. In addition, higher iAUC0–240 min for active GLP-1 was obtained with WD diet (WD: 2230 ± 441; BC: 925 ± 183 pM min/ml; P < 0⋅01). This study showed that WD can be used to replace a regular breakfast for improving postprandial glucose response and active GLP-1 levels in people with T2DM. Further studies are required to elucidate the clinical efficacy of WD on long-term glycaemic control in people with T2DM.
Deterministic and stochastic bifurcations in two-dimensional electroconvective flows

Abstract We investigate deterministic and stochastic bifurcations in electroconvecitve flows of a dielectric liquid confined between two parallel plates subjected to a strong unipolar injection by direct numerical simulations. A long-standing discrepancy of linear instability criteria between the experiment and theory exists in this flow. We here test the hypothesis that the discrepancy may be related to the inhomogeneity in ion-exchange membranes used in experiments, contrasted by the homogeneous ion injection assumed in theoretical and numerical analyses. To study this effect, we consider stochastic boundary conditions around linear criticality and first bifurcations in this flow. For a complete presentation of flow bifurcations, deterministic bifurcation analysis (without stochasticity) is first performed to investigate primary bifurcations in this flow by progressively increasing the strength of electric field. Lyapunov spectrum and dimension are calculated and probed to characterise the chaotic motion therein. Our results confirm the high dimensionality of chaos in electroconvective flows and reveal for the first time that its chaos is extensive in a range of finite-sized systems. We then conduct stochastic bifurcation analyses by considering random perturbations in the boundary conditions of charge density and electric potential. Owing to the subcritical nature of electroconvective flows, the linear instability criteria under stochastic boundaries are closer to the experimental values than former theoretical and numerical results (assuming the homogeneous charge injection) for different levels of stochasticity, which confirms the hypothesis aforementioned. Furthermore, stochasticity can also enhance the efficiency of ionic transport.
Brassica carinata biomass, yield, and seed chemical composition response to nitrogen rates and timing on southern Coastal Plain soils in the United States

Brassica carinata (carinata), a non‐food oilseed feedstock mainly used for biofuel, is a relatively new alternative winter crop in the southeastern (SE) United States (US). However, there are limited N rate and N application timing data available at the regional scale. These data are needed to expand production in the SE US. An N rate study was conducted during the winter–spring growing seasons during 2017–2018 and 2018–2019 in Florida, US, and at three locations during 2018–2019 in Georgia, US, to quantify the effects of N rate (0, 45, 90, 134, and 179 kg N ha−1) on carinata nutrient uptake, biomass, seed yield, and seed chemical composition. Seed yield showed a linear response up to 134 kg N ha−1. Seed protein and glucosinolate concentrations decreased from 0 to 90 kg N ha−1, then increased from 90 to 179 kg N ha−1. Seed oil concentration was inversely related to seed protein concentration. A two‐factor N application timing study (4 N application timing: at‐plant, pre‐bolting, at‐plant + pre‐bolting, at‐plant + pre‐bolting + bolting × 4 N rates: 0, 45, 90, and 134 kg N ha−1) was conducted in Georgia, US, over three site‐years to quantify the effect of N application timing on yield and agronomic and economic optimum N rates (AONR and EONR, respectively). All split applications increased AONR by at least 10 kg N ha−1 compared to a single at‐plant application. A two‐split N application was more profitable than either a single N application or a three‐split N application based on marginal return. A two‐way split application (at‐plant + pre‐bolting) at 134 kg N ha−1 is recommended to optimize yield and economical production. Based on uncertainty analyses, the 50% credible interval of EONR occurred between 116 and 152 kg N ha−1, with a median estimate at 130 kg N ha−1.